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3. List of contributors

Author

Ahmad, Abul H., primary, Akingbasote, James, additional, Anadón, Arturo, additional, Anand, Rashmi, additional, Anantharam, Vellareddy, additional, András, Csaba, additional, Ares, Irma, additional, Avdonin, Pavel V., additional, Ay, Muhammet, additional, Banerjee, Aryamitra, additional, Barnett, Reid E., additional, Belinskaia, Daria A., additional, Bertero, Alessia, additional, Bharti, Vijay K., additional, Bian, Wan-Ping, additional, Bischoff, Karyn L., additional, Caloni, Francesca, additional, Castela, Ana Catarina, additional, Chand, Naresh, additional, Chanderbhan, Ronald F., additional, Charli, Adhithiya, additional, Charrette, Andrew, additional, Chen, Si, additional, Chen, Tao, additional, Choudhuri, Supratim, additional, Choudhury, Soumen, additional, Coccini, Teresa, additional, Cope, Rhian B., additional, Coppock, Robert W., additional, Costa, Lucio G., additional, Damodaran, Tirupapuliyur, additional, Darvesh, Altaf S., additional, Dhruw, Leena, additional, Dormán, György, additional, Doss, Robin B., additional, DuBourdieu, Dan, additional, Dziwenka, Margitta, additional, Eades, Joshua, additional, Esch, Harald L., additional, Filazi, Ayhan, additional, Fitsanakis, Vanessa A., additional, Flachner, Beáta, additional, Fossati, Paola, additional, Gambaryan, Stepan P., additional, Garg, Ramesh C., additional, Garg, Satish K., additional, Gil, Fernando, additional, Goncharov, Nikolay V., additional, Gulati, Kavita, additional, Guo, Lei, additional, Guo, Xiaoqing, additional, Gupta, Bhanushree, additional, Gupta, Ramesh C., additional, Guthrie, Najla, additional, Gwaltney-Brant, Sharon M., additional, Hajdú, István, additional, Hartsel, Joshua A., additional, Hazzah, Trina, additional, Hernández, Antonio F., additional, Hickory, Brian, additional, Hilmas, Corey J., additional, Hoeng, Julia, additional, Jain, Amul, additional, Jenkins, Richard O., additional, Jin, Huajun, additional, Joshi, Jagdish Chandra, additional, Kalinovsky, Tatiana, additional, Kalpana, Starling, additional, Kalidindi, Sanyasi R., additional, Kanthasamy, Anumantha G., additional, Kanthasamy, Arthi, additional, Kaore, Navinchandra M., additional, Kaore, Shilpa N., additional, Kapoor, Vijay Kumar, additional, Kaur, Gurjot, additional, Kolanos, Renata, additional, Korf, Ekaterina A., additional, Krishna, Gopala, additional, Krishna, Mayur, additional, Kuča, Kamil, additional, Kudryavtsev, Igor V., additional, Kumar, Amit, additional, Kumar, Dinesh, additional, Kumar, Prafull, additional, Lall, Rajiv, additional, La Mesa, Camillo, additional, Latino, Diogo A.R.S., additional, Lehmann, Leane, additional, Li, Xilin, additional, Machado, Ivo F., additional, Makriyannis, Alexandros, additional, Malik, Jitendra K., additional, Martín-Domingo, M. Concepción, additional, Martínez, María-Aránzazu, additional, Martínez-Larrañaga, María-Rosa, additional, Mei, Nan, additional, Messinis, Dimitris E., additional, Mindukshev, Igor V., additional, Negi, Poonam, additional, Niedzwiecki, Aleksandra, additional, Ning, Baitang, additional, Novozhilov, Artem V., additional, Palmeira, Carlos Marques, additional, Papas, Andreas M., additional, Pei, De-Sheng, additional, Peitsch, Manuel C., additional, Peterson, Jeffrey D., additional, Pistollato, Francesca, additional, Pitt, Jason, additional, Pitt, Yiuka, additional, Pospisil, Pavel, additional, Poussin, Carine, additional, Pradhan, Aanchal, additional, Prakash, Atul, additional, Prasad, Sahdeo, additional, Rahal, Anu, additional, Rai, Nishant, additional, Raina, Rajinder, additional, Rath, Matthias, additional, Ray, Arunabha, additional, Rehman, Sana, additional, Richter, Gary, additional, Risuleo, Gianfranco, additional, Roberts, Ashley, additional, Rolo, Anabela Pinto, additional, Roomi, M. Waheed, additional, Sachana, Magdalini, additional, Satoh, Tetsuo, additional, Serebriakova, Maria K., additional, Sharma, Rahul, additional, Shukla, Amit, additional, Sinha, Anita, additional, Sinha, Priynak, additional, Spicer, Leon J, additional, Srivastava, Ajay, additional, Stice, Szabina A., additional, Sudnitsyna, Julia S., additional, Taku, Ila, additional, Talukder, Jamil, additional, Teodoro, João Soeiro, additional, Thokchom, Suresh Kumar, additional, Trulioff, Andrey S., additional, Ukolov, Anton I., additional, Umegaki, Keizo, additional, Verma, Pankaj, additional, Verma, Pawan K., additional, Wan, Dan, additional, Wilson-Frank, Christina, additional, Woldemeskel, Moges, additional, Wu, Qinghua, additional, Yang, Mildred S., additional, Yurdakok-Dikmen, Begum, additional, Zaja-Milatovic, Snjezana, additional, and Zoltani, Csaba K., additional

Published
2021
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12. Shaping of Hepatic Ischemia/Reperfusion Events: The Crucial Role of Mitochondria

Author

European Commission, Fundação para a Ciência e a Tecnologia (Portugal), Teodoro, João S., Teixeira da Silva, Rui, Machado, Ivo F., Panisello-Roselló, Arnau, Roselló-Catafau, Joan, Rolo, Anabela Pinto, Palmeira, Carlos M., European Commission, Fundação para a Ciência e a Tecnologia (Portugal), Teodoro, João S., Teixeira da Silva, Rui, Machado, Ivo F., Panisello-Roselló, Arnau, Roselló-Catafau, Joan, Rolo, Anabela Pinto, and Palmeira, Carlos M.

Abstract

Hepatic ischemia reperfusion injury (HIRI) is a major hurdle in many clinical scenarios, including liver resection and transplantation. Various studies and countless surgical events have led to the observation of a strong correlation between HIRI induced by liver transplantation and early allograft-dysfunction development. The detrimental impact of HIRI has driven the pursuit of new ways to alleviate its adverse effects. At the core of HIRI lies mitochondrial dysfunction. Various studies, from both animal models and in clinical settings, have clearly shown that mitochondrial function is severely hampered by HIRI and that its preservation or restoration is a key indicator of successful organ recovery. Several strategies have been thus implemented throughout the years, targeting mitochondrial function. This work briefly discusses some the most utilized approaches, ranging from surgical practices to pharmacological interventions and highlights how novel strategies can be investigated and implemented by intricately discussing the way mitochondrial function is affected by HIRI.

Published
2022

13. PEG35 as a Preconditioning Agent against Hypoxia/Reoxygenation Injury

Author

European Commission, Fundação para a Ciência e a Tecnologia (Portugal), Teixeira da Silva, Rui, Machado, Ivo F., Teodoro, João S., Panisello-Roselló, Arnau, Roselló-Catafau, Joan, Rolo, Anabela Pinto, Palmeira, Carlos M., European Commission, Fundação para a Ciência e a Tecnologia (Portugal), Teixeira da Silva, Rui, Machado, Ivo F., Teodoro, João S., Panisello-Roselló, Arnau, Roselló-Catafau, Joan, Rolo, Anabela Pinto, and Palmeira, Carlos M.

Abstract

Pharmacological conditioning is a protective strategy against ischemia/reperfusion injury, which occurs during liver resection and transplantation. Polyethylene glycols have shown multiple benefits in cell and organ preservation, including antioxidant capacity, edema prevention and membrane stabilization. Recently, polyethylene glycol 35 kDa (PEG35) preconditioning resulted in decreased hepatic injury and protected the mitochondria in a rat model of cold ischemia. Thus, the study aimed to decipher the mechanisms underlying PEG35 preconditioning-induced protection against ischemia/reperfusion injury. A hypoxia/reoxygenation model using HepG2 cells was established to evaluate the effects of PEG35 preconditioning. Several parameters were assessed, including cell viability, mitochondrial membrane potential, ROS production, ATP levels, protein content and gene expression to investigate autophagy, mitochondrial biogenesis and dynamics. PEG35 preconditioning preserved the mitochondrial function by decreasing the excessive production of ROS and subsequent ATP depletion, as well as by recovering the membrane potential. Furthermore, PEG35 increased levels of autophagy-related proteins and the expression of genes involved in mitochondrial biogenesis and fusion. In conclusion, PEG35 preconditioning effectively ameliorates hepatic hypoxia/reoxygenation injury through the enhancement of autophagy and mitochondrial quality control. Therefore, PEG35 could be useful as a potential pharmacological tool for attenuating hepatic ischemia/reperfusion injury in clinical practice.

Published
2022

17. Mitochondrial physiology: Gnaiger Erich et al ― MitoEAGLE Task Group

Author

Gnaiger, Erich, Aasander Frostner, Eleonor, Abdul Karim, Norwahidah, Abdel-Rahman, Engy Ali, Abumrad, Nada A, Acuna-Castroviejo, Dario, Adiele, Reginald C, Ahn, Bumsoo, Alencar, MB, Ali, Sameh S, Almeida, Angeles, Alton, Lesley, Alves, Marco G, Amati, Francesca, Amoedo, Nivea Dias, Amorim, Ricardo, Anderson, Ethan J, Andreadou, Ioanna, Antunes, Diana, Arago, Marc, Aral, Cenk, Arandarcikaite, Odeta, Arias-Reyes, Christian, Armand, Anne-Sophie, Arnould, Thierry, Avram, Vlad Florian, Axelrod, Christopher L, Bairam, Aida, Bailey, Damian M, Bajpeyi, Sudip, Bajzikova, Martina, Bakker, Barbara M, Barlow, Jonathan, Bardal, Tora, Banni, A, Bastos Sant'Anna Silva, Ana Carolina, Batterson, Philip, Battino, Maurizio, Bazil, Jason, Beard, Daniel A, Beleza, Jorge, Bednarczyk, Piotr, Bello, Fiona, Ben-Shachar, Dorit, Bento Guida, Jose Freitas, Bergdahl, Andreas, Berge, Rolf K, Bergmeister, Lisa, Bernardi, Paolo, Berridge, Michael V, Bettinazzi, Stefano, Bishop, David, Blier, Pierre U, Blindheim, Dan Filip, Boardman, Neoma T, Boetker, Hans Erik, Borchard, Sabine, Boros, Mihaly, Borsheim, Elisabet, Borras, Consuelo, Borutaite, Vilma, Botella, Javier, Bouillaud, Frederic, Bouitbir, Jamal, Boushel, Robert C, Bovard, Josh, Bravo-Sagua, Roberto, Breton, Sophie, Brown, David A, Brown, Guy C, Brown, Robert A, Brozinick, Joseph T, Buettner, Garry R, Burtscher, Johannes, Bustos, Matilde, Calabria, Elisa, Calbet, Jose A, Calzia, Enrico, Cannon, Daniel T, Cano Sanchez, Maria, Canto Alvarez, Carles, Cardinale, D, Cardoso, Luiza Helena Daltro, Carvalho, Eugenia, Casado Pinna, Marta, Cassar, Samantha, Castelo, Maria P, Castilho, Roger F, Cavalcanti-de-Albuquerque, Joao Paulo, Cecatto, Cristiane, Celen, Murat C, Cervinkova, Zuzana, Chabi, Beatrice, Chakrabarti, Lisa, Chakrabarti, Sasanka, Chaurasia, Bhagirath, Chen, Quan, Chicco, Adam J, Chinopoulos, Christos, Chowdhury, Subir K, Cizmarova, Beata, Clementi, Emilio, Coen, Paul M, Cohen, Bruce H, Coker, Robert H, Collin-Chenot, Anne, Coughlan, Melinda T, Coxito, Petro, Crisostomo, Luis, Crispim, Marcell, Crossland, Hannah, Dahdah, Norma, Dalgaard, Louise T, Dambrova, Maija, Danhelovska, Tereza, Darveau, Charles A, Darwin, Paula M, Das, Anibh M, Dash, Ranjan K, Davidova, Eliska, Davis, Michael S, Dayanidhi, Sudarshan, De Bem, Andreza Fabro, De Goede, Paul, De Palma, Clara, De Pinto, Vito, Dela, F, Dembinska-Kiec, Aldona, Detraux, Damien, Devaux, Yvan, Di Marcello, Marco, Di Paola, Floriana Jessica, Dias, Candida, Dias, Tania R, Diederich, Marc, Distefano, Giovanna, Djafarzadeh, Siamak, Doermann, Niklas, Doerrier, Carolina, Dong, Lan-Feng, Donnelly, Chris, Drahota, Zdenek, Duarte, Filipe Valente, Dubouchaud, Herve, Duchen, Michael R, Dumas, Jean-Francois, Durham, William J, Dymkowska, Dorota, Dyrstad, Sissel E, Dyson, Alex, Dzialowski, Edward M, Eaton, Simon, Ehinger, Johannes, Elmer, Eskil, Endlicher, Rene, Engin, Ayse B, Escames, Germaine, Evinova, Andrea, Ezrova, Zuzana, Falk, Marni Joy, Fell, David A, Ferdinandy, Peter, Ferko, Miroslav, Fernandez-Ortiz, Marisol, Erika, Fernandez-Vizarra, Ferreira, Julio Cesar Batista, Ferreira, Rita, Ferri, Alessandra, Festuccia, WT, Fessel, Joshua P, Filipovska, Aleksandra, Fisar, Zdenek, Fischer, Christine, Fischer, Michael, Fisher, Gordon, Fisher, Joshua J, Fontanesi, Flavia, Forbes-Hernandez, Tamara Y, Ford, Ellen, Fornaro, Mara, Fuertes Agudo, Marina, Fulton, Montana, Galina, Antonio, Galkin, Alexander, Gallee, Leon, Galli, Gina L, Gama Perez, Pau, Gan, Zhenji, Ganetzky, Rebecca, Gao, Yun, Garcia, Geovana S, Garcia-Rivas, Gerardo, Garcia-Roves, Pablo Miguel, Garcia-Souza, Luiz Felipe, Garlid, Keith D, Garrabou, Gloria, Garten, Antje, Gastaldelli, Amalia, Gayen, Jiaur, Genders, Amanda J, Genova, Maria Luisa, Giampieri, Francesca, Glatz, Jan FC, Giovarelli, Matteo, Goikoetxea Usandizaga, Naroa, Goncalo Teixeira da Silva, Rui, Goncalves, Debora Farina, Gonzalez-Armenta, Jenny L, Gonzalez-Francesqua, A, Gonzalez-Freire, Marta, Gonzalo, Hugo, Goodpaster, Bret H, Gorr, Thomas A, Gourlay, Campbell W, Grams, Bente, Granata, Cesare, Grefte, Sander, Grilo, Luis, Guarch, Meritxell Espino, Gueguen, Naig, Gumeni, Sentiljana, Haas, Clarissa B, Haavik, Jan, Hachmo, Yafit, Haendeler, Judith, Haider, Markus, Hajrulahovic, Anesa, Hamann, Andrea, Han, Jin, Han, Woo Hyun, Hancock, Chad R, Hand, Steven C, Handl, Jiri, Hansikova, Hana, Hardee, Justin P, Hargreaves, Ian P, Harper, Mary Ellen, Harrison, David K, Hassan, Hazirah, Hatakova, Zuzana, Hausenloy, Derek J, Heales, Simon JR, Heiestad, Christina, Hellgren, Kim T, Henrique, Alexandrino, Hepple, Russell T, Hernansanz-Agustin, Pablo, Hewakapuge, Sudinna, Hickey, Anthony J, Ho, Dieu Hien, Hoehn, Kyle L, Hoel, Frederik, Holland, Olivia J, Holloway, Graham P, Holzner, Lorenz, Hoppel, Charles L, Hoppeler, H, Hoppel, Florian, Houstek, Josef, Huete-Ortega, Maria, Hyrossova, Petra, Iglesias-Gonzalez, Javier, Indiveri, Cesare, Irving, Brian A, Isola, Raffaella, Iyer, Shilpa, Jackson, Christophe B, Jadiya, Pooja, Jana, Prado Fabian, Jandeleit-Dahm, K, Jang, David H, Jang, Young C, Janowska, Joanna, Jansen, Kirsten, Jansen-Duerr, Pidder, Jansone, Baiba, Jarmuszkiewicz, Wieslawa, Jaskiewicz, Anna, Jaspers, Richard T, Jedlicka, Jan, Jerome, Estaquier, Jespersen, Nichlas R, Jha, Rajan K, Joseph, Vincent, Juhasz, Laszlo, Jurczak, Michael J, Jurk, Diana, Kaambre, Tuuli, Kaczor, Jan J, Kainulainen, Heikki, Kampa, Rafal Pawel, Kandel, Sunil M, Kane, Daniel A, Kapferer, Werner, Kapnick, Senta, Kappler, Lisa, Karabatsiakis, Alexander, Karavaeva, Iuliia, Karkucinska-Wieckowska, Agnieszka, Kaur, Sarbjot, Keijer, Jaap, Keller, Markus A, Keppner, Gloria, Khamoui, Andy V, Kidere, Dita, Kilbaugh, Todd, Kim, Hyoung Kyu, Kim, Julian KS, Kimoloi, Sammy, Klepinin, Aleksandr, Klepinina, Lyudmila, Klingenspor, Martin, Klocker, Helmut, Komlódi, Timea, Kolasa, Iris, Koopman, Werner JH, Kopitar-Jerala, Natasa, Kowaltowski, Alicia J, Kozlov, Andrey V, Krajcova, Adela, Krako Jakovljevic, Nina, Kristal, Bruce S, Krycer, Jamer R, Kuang, Jujiao, Kucera, Otto, Kuka, Janis, Kwak, Hyo Bum, Kwast, Kurt, Kwon, Oh Sung, Laasmaa, Martin, Labieniec-Watala, Magdalena, Lai, Nicola, Lalic, Nebojsa M, Land, John M, Lane, Nick, Laner, Verena, Lanza, Ian R, Laouafa, Sofien, Larsen, Steen, Larsen, Terje S, Lavery, Gareth G, Lazou, Antigone, Ledo, Ana Margarida, Lee, Hong Kyu, Leeuwenburgh, Christiaan, Lehti, Maarit, Lemieux, Helene, Lenaz, Giorgio, Lerfall, Jorgen, Li, Pingan A, Li Puma, Lance, Liang, Liping, Liepins, Edgars, Lin, Chien-Te, Liu, Jiankang, Lopez, Luis C, Lucchinetti, Eliana, Ma, Tao, Macedo, Maria P, Machado, Ivo F, Maciej, Sarah, MacMillan-Crow, Lee Ann, Magalhaes, Jose, Magri, Andrea, Majtnerova, Pavlina, Makarova, Elina, Makrecka-Kuka, Marina, Malik, Afshan N, Marcouiller, Francois, Marechal, Amandine, Markova, Michaela, Markovic, Ivanka, Martin, Daniel S, Martins, Ana Dias, Martins, Joao D, Maseko, Tumisang Edward, Maull, Felicia, Mazat, Jean Pierre, McKenna, Helen T, McKenzie, Matthew, McMillan, Duncan GG, McStay, Gavin P, Menze, Michael A, Mendham, Amy, Mercer, John R, Merz, Tamara, Messina, Angela, Meszaros, Andras T, Methner, Axel, Michalak, Slawomir, Mila Guasch, Maria, Minuzzi, Luciele M, Misirkic Marjanovic, Maja, Moellering, Douglas R, Moisoi, Nicoleta, Molina, Anthony JA, Montaigne, David, Moore, Anthony L, Moore, Christy, Moreau, Kerrie, Moreira, Bruno P, Moreno-Sanchez, Rafael, Mracek, Tomas, Muccini, Anna Maria, Muntane, Jordi, Muntean, Danina M, Murray, Andrew J, Musiol, Eva, Nabben, Miranda, Nair, K Sreekumaran, Nehlin, Jan O, Nemec, Michal, Nesci, Salvatore, Neufer, P Darrell, Neuzil, Jiri, Neviere, Remi, Newsom, Sean A., Norman, Jennifer, Nozickova, Katerina, Nunes, Sara, Nuoffer, Jean-Marc, O'Brien, Kristin, O'Brien, Katie A, O'Gorman, Donal, Olgar, Yusuf, Oliveira, Ben, Oliveira, Jorge, Oliveira, Marcus F, Oliveira, Marcos Tulio, Oliveira, Pedro F, Oliveira, Paulo J, Olsen, Rolf Erik, Orynbayeva, Zulfiya, Osiewacz, Heinz D, Paez, Hector, Pak, Youngmi K, Pallotta, Maria L, Palmeira, Carlos M, Parajuli, Nirmala, Passos, Joao F, Passrugger, Manuela, Patel, Hemal H, Pavlova, Nadia, Pavlovic, Kasja, Pecina, Petr, Pedersen, Tina M, Perales, Jose Carlos, Pereira da Silva Grilo da Silva, Filomena, Pereira, Rita, Perez Valencia, Juan A, Perks, Kara L, Pesta, Dominik, Petit, Patrice X, Pettersen Nitschke, Ina Katrine, Pichaud, Nicolas, Pichler, Irene, Piel, Sarah, Pietka, Terri A, Pinho, Sonia A, Pino, Maria F, Pirkmajer, Sergej, Place, Nicolas, Plangger, Mario, Porter, Craig, Porter, Richard K, Preguica, Ines, Procaccio, Vincent, Prochownik, Edward V, Prola, Alexandre, Pulinilkunnil, Thomas, Puskarich, Michael A, Puurand, Marju, Radenkovic, Filip, Ramzan, Rabia, Rattan, Suresh IS, Reano, Simone, Reboredo, Patricia, Rees, Bernard B, Renner-Sattler, Kathrin, Rial, Eduardo, Robinson, Matthew M, Roden, Michael, Rodrigues, Ana Sofia, Rodriguez, Enrique, Rodriguez-Enriquez, Sara, Roesland, Gro Vatne, Rolo, Anabela Pinto, Ropelle, Eduardo R, Roshanravan, Baback, Rossignol, Rodrigue, Rossiter, Harry B, Rousar, Tomas, Rubelj, Ivica, Rybacka-Mossakowska, Joanna, Saada, Ann, Safaei, Zahra, Sarlak, Saharnaz, Salin, Karine, Salvadego, Desy, Sandi, Carmen, Saner, Nicholas, Santos, Diana, Sanz, Alberto, Sardao, Vilma, Sazanov, Leonid A, Scaife, Paula, Scatena, Roberto, Schartner, Melanie, Scheibye-Knudsen, Morten, Schilling, Jan M, Schlattner, Uwe, Schmitt, Sabine, Schneider Gasser, Edith Mariane, Schoenfeld, Peter, Schots, Pauke C, Schulz, Rainer, Schwarzer, Christoph, Scott, Graham R, Selman, Colin, Sendon, Pamella Marie, Shabalina, Irina G, Sharma, Pushpa, Sharma, Vipin, Shevchuk, Igor, Shirazi, Reza, Shiroma, Jonathan G, Siewiera, Karolina, Silber, Ariel M, Silva, Ana Maria, Sims, Carrie A, Singer, Dominique, Singh, Brijesh Kumar, Skolik, Robert A, Smenes, Benedikte Therese, Smith, James, Soares, Félix Alexandre Antunes, Sobotka, Ondrej, Sokolova, Inna, Solesio Torregrosa, M De la Encarnacion, Soliz, Jorge, Sonkar, Vijay K, Sova, Marina, Sowton, Alice P, Sparagna, Genevieve C, Sparks, Lauren M, Spinazzi, Marco, Stankova, Pavla, Starr, Jonathan, Stary, Creed, Stefan, Eduard, Stelfa, Gundega, Stepto, Nigel K, Stevanovic, Jelena, Stiban, Johnny, Stier, Antoine, Stocker, Roland, Storder, Julie, Sumbalova, Zuzana, Suomalainen, Wartiovaara Anu, Suravajhala, Prashanth, Svalbe, Baiba, Swerdlow, Russel H, Swiniuch, Daria, Szabo, Ildiko, Szewczyk, Adam, Szibor, Marten, Tanaka, Masashi, Tandler, Bernard, Tarnopolsky, Mark A, Tausan, Daniel, Tavernarakis, Nektarios, Tepp, Kersti, Teodoro, J, Thakkar, Himani, Thapa, Maheshwo, Thyfault, John P, Tomar, Dhanendra, Ton, Riccardo, Torp, May-Kristin, Torres-Quesada, Omar, Towheed, Atif, Treberg, Jason R, Tretter, Laszlo, Trewin, Adam J, Trifunovic, Aleksandra, Trivigno, Catherine, Tronstad, Karl Johan, Trougakos, Ioannis P, Truu, Laura, Tuncay, Erkan, Turan, Belma, Tyrrell, Daniel J, Urban, Tomas, Urner, Sofia, Valentine, Joseph Marco, Van Bergen, Nicole J, Van der Ende, Miranda, Varricchio, Frederick, Vaupel, Peter, Vella, Joanna, Vendelin, Marko, Verdaguer, IB, Vercesi, Anibal E, Vernerova, Andrea, Victor, Victor Manuel, Vieira Ligo Teixeira, Camila, Vidimce, Josif, Viel, Christian, Vieyra, Adalberto, Vilks, Karlis, Villena, Joseph A, Vincent, Vinnyfred, Vinogradov, Andrey D, Viscomi, Carlo, Vitorino, Rui Miguel Pinheiro, Vlachaki Walker, Julia, Vogt, Sebastian, Volani, Chiara, Volska, Kristine, Votion, Dominique-Marie, Vujacic-Mirski, Ksenija, Wagner, Brett A, Ward, Marie Louise, Warnsmann, Verena, Wasserman, David H, Watala, Cezary, Wei, Yau-Huei, Weinberger, Klaus M, White, Sarah, Whitfield, Jamie, Wickert, Anika, Wieckowski, Mariusz R, Wiesner, Rudolf J, Williams, Caroline M, Winwood-Smith, Hugh, Wohlgemuth, Stephanie E, Wohlwend, Martin, Wolff, Jonci Nikolai, Wrutniak-Cabello, Chantal, Wuest, Rob C I, Yokota, Takashi, Zablocki, Krzysztof, Zanon, Alessandra, Zanou, Nadege, Zaugg, Kathrin, Zaugg, Michael, Zdrazilova, Lucie, Zhang, Yong, Zhang, Yi Zhu, Zikova, Alena, Zischka, Hans, Zorzano, Antonio, Zujovic, Tijana, Zurmanova, Jitka, Zvejniece, Liga, Lagarrigue, Sylviane, Munro, Daniel, Pereira, Susana, Laranjinha, Joäo, Hecker, Matthias, Jusic, Amela, Prigione, Alessandro, Sommer, Natascha, Weissig, Volkmar, Guida, Bento, G, John G, Jones, JG, AMS - Tissue Function & Regeneration, AMS - Rehabilitation & Development, Physiology, Mito-Eagle - Evolution-Age-Gender-Lifestyle-Environment (Mito-Eagle), Oroboros Instruments, Dynamique Musculaire et Métabolisme (DMEM), Université de Montpellier (UM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and Gnaiger Erich, Aasander Frostner Eleonor, Abdul Karim Norwahidah, Abdel-Rahman Engy Ali, Abumrad Nada A, Acuna-Castroviejo Dario, Adiele Reginald C, Ahn Bumsoo, Alencar Mayke Bezerra, Ali Sameh S, Almeida Angeles, Alton Lesley, Alves Marco G, Amati Francesca, Amoedo Nivea Dias, Amorim Ricardo, Anderson Ethan J, Andreadou Ioanna, Antunes Diana, Arago Marc, Aral Cenk, Arandarcikaite Odeta, Arias-Reyes Christian, Armand Anne-Sophie, Arnould Thierry, Avram Vlad F, Axelrod Christopher L, Bailey Damian M, Bairam Aida, Bajpeyi Sudip, Bajzikova Martina, Bakker Barbara M, Banni Aml, Bardal Tora, Barlow J, Bastos Sant'Anna Silva Ana Carolina, Batterson Philip M, Battino Maurizio, Bazil Jason N, Beard Daniel A, Bednarczyk Piotr, Beleza Jorge, Bello Fiona, Ben-Shachar Dorit, Bento Guida Jose Freitas, Bergdahl Andreas, Berge Rolf K, Bergmeister Lisa, Bernardi Paolo, Berridge Michael V, Bettinazzi Stefano, Bishop David J, Blier Pierre U, Blindheim Dan Filip, Boardman Neoma T, Boetker Hans Erik, Borchard Sabine, Boros Mihaly, Boersheim Elisabet, Borras Consuelo, Borutaite Vilma, Botella Javier, Bouillaud Frederic, Bouitbir Jamal, Boushel Robert C, Bovard Josh, Bravo-Sagua Roberto, Breton Sophie, Brown David A, Brown Guy C, Brown Robert Andrew, Brozinick Joseph T, Buettner Garry R, Burtscher Johannes, Bustos Matilde, Calabria Elisa, Calbet Jose AL, Calzia Enrico, Cannon Daniel T, Cano Sanchez Maria Consolacion, Canto Alvarez Carles, Cardinale Daniele A, Cardoso Luiza HD, Carvalho Eugenia, Casado Pinna Marta, Cassar Samantha, Castelo Rueda Maria Paulina, Castilho Roger F, Cavalcanti-de-Albuquerque Joao Paulo, Cecatto Cristiane, Celen Murat C, Cervinkova Zuzana, Chabi Beatrice, Chakrabarti Lisa, Chakrabarti Sasanka, Chaurasia Bhagirath, Chen Quan, Chicco Adam J, Chinopoulos Christos, Chowdhury Subir Kumar, Cizmarova Beata, Clementi Emilio, Coen Paul M, Cohen Bruce H, Coker Robert H, Collin-Chenot Anne, Coughlan Melinda T, Coxito Pedro, Crisostomo Luis, Crispim Marcell, Crossland Hannah, Dahdah Norma Ramon, Dalgaard Louise T, Dambrova Maija, Danhelovska Tereza, Darveau Charles-A, Darwin Paula M, Das Anibh Martin, Dash Ranjan K, Davidova Eliska, Davis Michael S, Dayanidhi Sudarshan, De Bem Andreza Fabro, De Goede Paul, De Palma Clara, De Pinto Vito, Dela Flemming, Dembinska-Kiec Aldona, Detraux Damian, Devaux Yvan, Di Marcello Marco, Di Paola Floriana Jessica, Dias Candida, Dias Tania R, Diederich Marc, Distefano Giovanna, Djafarzadeh Siamak, Doermann Niklas, Doerrier Carolina, Dong Lan-Feng, Donnelly Chris, Drahota Zdenek, Duarte Filipe Valente, Dubouchaud Herve, Duchen Michael R, Dumas Jean-Francois, Durham William J, Dymkowska Dorota, Dyrstad Sissel E, Dyson Alex, Dzialowski Edward M, Eaton Simon, Ehinger Johannes K, Elmer Eskil, Endlicher Rene, Engin Ayse Basak, Escames Germaine, Evinova Andrea, Ezrova Zuzana, Falk Marni J, Fell David A, Ferdinandy Peter, Ferko Miroslav, Fernandez-Ortiz Marisol, Fernandez-Vizarra Erika, Ferreira Julio Cesar B, Ferreira Rita Maria P, Ferri Alessandra, Fessel Joshua Patrick, Festuccia William T, Filipovska Aleksandra, Fisar Zdenek, Fischer Christine, Fischer Michael J, Fisher Gordon, Fisher Joshua J, Fontanesi Flavia, Forbes-Hernandez Tamara Y, Ford Ellen, Fornaro Mara, Fuertes Agudo Marina, Fulton Montana, Galina Antonio, Galkin Alexander, Gallee Leon, Galli Gina L J, Gama Perez Pau, Gan Zhenji, Ganetzky Rebecca, Gao Yun, Garcia Geovana S, Garcia-Rivas Gerardo, Garcia-Roves Pablo Miguel, Garcia-Souza Luiz F, Garlid Keith D, Garrabou Gloria, Garten Antje, Gastaldelli Amalia, Gayen Jiaur, Genders Amanda J, Genova Maria Luisa, Giampieri Francesca, Giovarelli Matteo, Glatz Jan FC, Goikoetxea Usandizaga Naroa, Goncalo Teixeira da Silva Rui, Goncalves Debora Farina, Gonzalez- Armenta Jenny L, Gonzalez-Franquesa Alba, Gonzalez-Freire Marta, Gonzalo Hugo, Goodpaster Bret H, Gorr Thomas A, Gourlay Campbell W, Grams Bente, Granata Cesare, Grefte Sander, Grilo Luis, Guarch Meritxell Espino, Gueguen Naig, Gumeni Sentiljana, Haas Clarissa, Haavik Jan, Hachmo Yafit, Haendeler Judith, Haider Markus, Hajrulahovic Anesa, Hamann Andrea, Han Jin, Han Woo Hyun, Hancock Chad R, Hand Steven C, Handl Jiri, Hansikova Hana, Hardee Justin P, Hargreaves Iain P, Harper Mary- Ellen, Harrison David K, Hassan Hazirah, Hatokova Zuzana, Hausenloy Derek J, Heales Simon JR, Hecker Matthias, Heiestad Christina, Hellgren Kim T, Henrique Alexandrino, Hepple Russell T, Hernansanz- Agustin Pablo, Hewakapuge Sudinna, Hickey Anthony J, Ho Dieu Hien, Hoehn Kyle L, Hoel Fredrik, Holland Olivia J, Holloway Graham P, Holzner Lorenz, Hoppel Charles L, Hoppel Florian, Hoppeler Hans, Houstek Josef, Huete-Ortega Maria, Hyrossova Petra, Iglesias-Gonzalez Javier, Indiveri Cesare, Irving Brian A, Isola Raffaella, Iyer Shilpa, Jackson Christopher Benjamin, Jadiya Pooja, Jana Prado Fabian, Jandeleit-Dahm Karin, Jang David H, Jang Young Charles, Janowska Joanna, Jansen Kirsten M, Jansen-Duerr Pidder, Jansone Baiba, Jarmuszkiewicz Wieslawa, Jaskiewicz Anna, Jaspers Richard T, Jedlicka Jan, Jerome Estaquier, Jespersen Nichlas Riise, Jha Rajan Kumar, Jones John G, Joseph Vincent, Juhasz Laszlo, Jurczak Michael J, Jurk Diana, Jusic Amela, Kaambre Tuuli, Kaczor Jan Jacek, Kainulainen Heikki, Kampa Rafal Pawel, Kandel Sunil Mani, Kane Daniel A, Kapferer Werner, Kapnick Senta, Kappler Lisa, Karabatsiakis Alexander, Karavaeva Iuliia, Karkucinska-Wieckowska Agnieszka, Kaur Sarbjot, Keijer Jaap, Keller Markus A, Keppner Gloria, Khamoui Andy V, Kidere Dita, Kilbaugh Todd, Kim Hyoung Kyu, Kim Julian KS, Kimoloi Sammy, Klepinin Aleksandr, Klepinina Lyudmila, Klingenspor Martin, Klocker Helmut, Kolassa Iris, Komlodi Timea, Koopman Werner JH, Kopitar-Jerala Natasa, Kowaltowski Alicia J, Kozlov Andrey V, Krajcova Adela, Krako Jakovljevic Nina, Kristal Bruce S, Krycer James R, Kuang Jujiao, Kucera Otto, Kuka Janis, Kwak Hyo Bum, Kwast Kurt E, Kwon Oh Sung, Laasmaa Martin, Labieniec-Watala Magdalena, Lagarrigue Sylviane, Lai Nicola, Lalic Nebojsa M, Land John M, Lane Nick, Laner Verena, Lanza Ian R, Laouafa Sofien, Laranjinha Joao, Larsen Steen, Larsen Terje S, Lavery Gareth G, Lazou Antigone, Ledo Ana Margarida, Lee Hong Kyu, Leeuwenburgh Christiaan, Lehti Maarit, Lemieux Helene, Lenaz Giorgio, Lerfall Joergen, Li Pingan Andy, Li Puma Lance, Liang Liping, Liepins Edgars, Lin Chien-Te, Liu Jiankang, Lopez Garcia Luis Carlos, Lucchinetti Eliana, Ma Tao, Macedo Maria Paula, Machado Ivo F, Maciej Sarah, MacMillan-Crow Lee Ann, Magalhaes Jose, Magri Andrea, Majtnerova Pavlina, Makarova Elina, Makrecka-Kuka Marina, Malik Afshan N, Marcouiller Francois, Marechal Amandine, Markova Michaela, Markovic Ivanka, Martin Daniel S, Martins Ana Dias, Martins Joao D, Maseko Tumisang Edward, Maull Felicia, Mazat Jean-Pierre, McKenna Helen T, McKenzie Matthew, McMillan Duncan GG, McStay Gavin P, Mendham Amy, Menze Michael A, Mercer John R, Merz Tamara, Messina Angela, Meszaros Andras, Methner Axel, Michalak Slawomir, Mila Guasch Maria, Minuzzi Luciele M, Misirkic Marjanovic Maja, Moellering Douglas R, Moisoi Nicoleta, Molina Anthony JA, Montaigne David, Moore Anthony L, Moore Christy, Moreau Kerrie, Moreira Bruno P, Moreno-Sanchez Rafael, Mracek Tomas, Muccini Anna Maria, Munro Daniel, Muntane Jordi, Muntean Danina M, Murray Andrew James, Musiol Eva, Nabben Miranda, Nair K Sreekumaran, Nehlin Jan O, Nemec Michal, Nesci Salvatore, Neufer P Darrell, Neuzil Jiri, Neviere Remi, Newsom Sean A, Norman Jennifer, Nozickova Katerina, Nunes Sara, Nuoffer Jean-Marc, O'Brien Kristin, O'Brien Katie A, O'Gorman Donal, Olgar Yusuf, Oliveira Ben, Oliveira Jorge, Oliveira Marcus F, Oliveira Marcos Tulio, Oliveira Pedro Fontes, Oliveira Paulo J, Olsen Rolf Erik, Orynbayeva Zulfiya, Osiewacz Heinz D, Paez Hector, Pak Youngmi Kim, Pallotta Maria Luigia, Palmeira Carlos, Parajuli Nirmala, Passos Joao F, Passrugger Manuela, Patel Hemal H, Pavlova Nadia, Pavlovic Kasja, Pecina Petr, Pedersen Tina M, Perales Jose Carles, Pereira da Silva Grilo da Silva Filomena, Pereira Rita, Pereira Susana P, Perez Valencia Juan Alberto, Perks Kara L, Pesta Dominik, Petit Patrice X, Pettersen Nitschke Ina Katrine, Pichaud Nicolas, Pichler Irene, Piel Sarah, Pietka Terri A, Pinho Sonia A, Pino Maria F, Pirkmajer Sergej, Place Nicolas, Plangger Mario, Porter Craig, Porter Richard K, Preguica Ines, Prigione Alessandro, Procaccio Vincent, Prochownik Edward V, Prola Alexandre, Pulinilkunnil Thomas, Puskarich Michael A, Puurand Marju, Radenkovic Filip, Ramzan Rabia, Rattan Suresh IS, Reano Simone, Reboredo-Rodriguez Patricia, Rees Bernard B, Renner-Sattler Kathrin, Rial Eduardo, Robinson Matthew M, Roden Michael, Rodrigues Ana Sofia, Rodriguez Enrique, Rodriguez-Enriquez Sara, Roesland Gro Vatne, Rohlena Jakub, Rolo Anabela Pinto, Ropelle Eduardo R, Roshanravan Baback, Rossignol Rodrigue, Rossiter Harry B, Rousar Tomas, Rubelj Ivica, Rybacka-Mossakowska Joanna, Saada Reisch Ann, Safaei Zahra, Salin Karine, Salvadego Desy, Sandi Carmen, Saner Nicholas, Santos Diana, Sanz Alberto, Sardao Vilma, Sarlak Saharnaz, Sazanov Leonid A, Scaife Paula, Scatena Roberto, Schartner Melanie, Scheibye-Knudsen Morten, Schilling Jan M, Schlattner Uwe, Schmitt Sabine, Schneider Gasser Edith Mariane, Schoenfeld Peter, Schots Pauke C, Schulz Rainer, Schwarzer Christoph, Scott Graham R, Selman Colin, Sendon Pamella Marie, Shabalina Irina G, Sharma Pushpa, Sharma Vipin, Shevchuk Igor, Shirazi Reza, Shiroma Jonathan G, Siewiera Karolina, Silber Ariel M, Silva Ana Maria, Sims Carrie A, Singer Dominique, Singh Brijesh Kumar, Skolik Robert A, Smenes Benedikte Therese, Smith James, Soares Felix Alexandre Antunes, Sobotka Ondrej, Sokolova Inna, Solesio Maria E, Soliz Jorge, Sommer Natascha, Sonkar Vijay K, Sova Marina, Sowton Alice P, Sparagna Genevieve C, Sparks Lauren M, Spinazzi Marco, Stankova Pavla, Starr Jonathan, Stary Creed, Stefan Eduard, Stelfa Gundega, Stepto Nigel K, Stevanovic Jelena, Stiban Johnny, Stier Antoine, Stocker Roland, Storder Julie, Sumbalova Zuzana, Suomalainen Anu, Suravajhala Prashanth, Svalbe Baiba, Swerdlow Russell H, Swiniuch Daria, Szabo Ildiko, Szewczyk Adam, Szibor Marten, Tanaka Masashi, Tandler Bernard, Tarnopolsky Mark A, Tausan Daniel, Tavernarakis Nektarios, Teodoro Joao Soeiro, Tepp Kersti, Thakkar Himani, Thapa Maheshwor, Thyfault John P, Tomar Dhanendra, Ton Riccardo, Torp May-Kristin, Torres-Quesada Omar, Towheed Atif, Treberg Jason R, Tretter Laszlo, Trewin Adam J, Trifunovic Aleksandra, Trivigno Catherine, Tronstad Karl Johan, Trougakos Ioannis P, Truu Laura, Tuncay Erkan, Turan Belma, Tyrrell Daniel J, Urban Tomas, Urner Sofia, Valentine Joseph Marco, Van Bergen Nicole J, Van der Ende Miranda, Varricchio Frederick, Vaupel Peter, Vella Joanna, Vendelin Marko, Vercesi Anibal E, Verdaguer Ignasi Bofill, Vernerova Andrea, Victor Victor Manuel, Vieira Ligo Teixeira Camila, Vidimce Josif, Viel Christian, Vieyra Adalberto, Vilks Karlis, Villena Josep A, Vincent Vinnyfred, Vinogradov Andrey D, Viscomi Carlo, Vitorino Rui Miguel Pinheiro, Vlachaki Walker Julia, Vogt Sebastian, Volani Chiara, Volska Kristine, Votion Dominique-Marie, Vujacic-Mirski Ksenija, Wagner Brett A, Ward Marie Louise, Warnsmann Verena, Wasserman David H, Watala Cezary, Wei Yau-Huei, Weinberger Klaus M, Weissig Volkmar, White Sarah Haverty, Whitfield Jamie, Wickert Anika, Wieckowski Mariusz R, Wiesner Rudolf J, Williams Caroline M, Winwood-Smith Hugh, Wohlgemuth Stephanie E, Wohlwend Martin, Wolff Jonci Nikolai, Wrutniak-Cabello Chantal, Wuest Rob CI, Yokota Takashi, Zablocki Krzysztof, Zanon Alessandra, Zanou Nadege, Zaugg Kathrin, Zaugg Michael, Zdrazilova Lucie, Zhang Yong, Zhang Yizhu, Zikova Alena, Zischka Hans, Zorzano Antonio, Zujovic Tijana, Zurmanova Jitka, Zvejniece Liga

Subjects
uncoupling, MitoPedia: Respiratory states, SI - The International System of Units, IUPAC, Coupling control, Mitochondrial preparations, Protonmotive force, Uncoupling, Oxidative phosphorylation, Phosphorylation efficiency, Electron transfer-pathway, LEAK-respiration, Residual oxygen consumption, Normalization of rate, Flow, Flux, Flux control ratio, Mitochondrial marker, Cell count, Oxygen, [SDV]Life Sciences [q-bio], coupling control, protonmotive force, oxidative phosphorylation, mitochondrial respiratory control, State 4, electron transfer, State 2, State 3, Mitochondrial physiology, residual oxygen consumption, flux, normalization, ion leak and slip compensatory state, efficiency, electron transfer system, flow, mitochondrial physiology, oxygen, mitochondrial preparations, proton leak
Abstract

As the knowledge base and importance of mitochondrial physiology to evolution, health and diseaseexpands, the necessity for harmonizing the terminologyconcerning mitochondrial respiratory states and rates has become increasingly apparent. Thechemiosmotic theoryestablishes the mechanism of energy transformationandcoupling in oxidative phosphorylation. Theunifying concept of the protonmotive force providestheframeworkfordeveloping a consistent theoretical foundation ofmitochondrial physiology and bioenergetics.We followthe latest SI guidelines and those of the International Union of Pure and Applied Chemistry(IUPAC)onterminology inphysical chemistry, extended by considerationsofopen systems and thermodynamicsof irreversible processes.Theconcept-driven constructive terminology incorporates the meaning of each quantity and alignsconcepts and symbols withthe nomenclature of classicalbioenergetics. We endeavour to provide a balanced view ofmitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes.Uniform standards for evaluation of respiratory states and rates will ultimatelycontribute BEC 2020.1 doi:10.26124/bec:2020-0001.v1www.bioenergetics-communications.org3of 44to reproducibility between laboratories and thussupport the development of datarepositoriesof mitochondrial respiratory function in species, tissues, and cells.Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery.

Published
2020
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18. Role of aldehyde dehydrogenase 2 in ischemia reperfusion injury: an update

Author

Instituto de Salud Carlos III, European Commission, Panisello-Roselló, Arnau [0000-0003-2062-6134], López, Alexandre [0000-0001-8978-4486], Folch-Puy, Emma[0000-0002-6277-9027], Carbonell, Teresa [0000-0002-7131-3667], Rolo, Anabela Pinto [0000-0003-3535-9630], Palmeira, Carlos M. [0000-0002-2639-7697], Net, Marc [0000-0003-0906-6404], Roselló-Catafau, Joan [0000-0001-7127-4883], Panisello-Roselló, Arnau, López, Alexandre, Folch-Puy, Emma, Carbonell, Teresa, Rolo, Anabela Pinto, Palmeira, Carlos M., Adam, René, Net, Marc, Roselló-Catafau, Joan, Instituto de Salud Carlos III, European Commission, Panisello-Roselló, Arnau [0000-0003-2062-6134], López, Alexandre [0000-0001-8978-4486], Folch-Puy, Emma[0000-0002-6277-9027], Carbonell, Teresa [0000-0002-7131-3667], Rolo, Anabela Pinto [0000-0003-3535-9630], Palmeira, Carlos M. [0000-0002-2639-7697], Net, Marc [0000-0003-0906-6404], Roselló-Catafau, Joan [0000-0001-7127-4883], Panisello-Roselló, Arnau, López, Alexandre, Folch-Puy, Emma, Carbonell, Teresa, Rolo, Anabela Pinto, Palmeira, Carlos M., Adam, René, Net, Marc, and Roselló-Catafau, Joan

Abstract

Aldehyde dehydrogenase 2 (ALDH2) is best known for its critical detoxifying role in liver alcohol metabolism. However, ALDH2 dysfunction is also involved in a wide range of human pathophysiological situations and is associated with complications such as cardiovascular diseases, diabetes mellitus, neurodegenerative diseases and aging. A growing body of research has shown that ALDH2 provides important protection against oxidative stress and the subsequent loading of toxic aldehydes such as 4-hydroxy-2-nonenal and adducts that occur in human diseases, including ischemia reperfusion injury (IRI). There is increasing evidence of its role in IRI pathophysiology in organs such as heart, brain, small intestine and kidney; however, surprisingly few studies have been carried out in the liver, where ALDH2 is found in abundance. This study reviews the role of ALDH2 in modulating the pathways involved in the pathophysiology of IRI associated with oxidative stress, autophagy and apoptosis. Special emphasis is placed on the role of ALDH2 in different organs, on therapeutic “preconditioning” strategies, and on the use of ALDH2 agonists such as Alda-1, which may become a useful therapeutic tool for preventing the deleterious effects of IRI in organ transplantation.

Published
2018

20. HepG2 spheroids cultured in alginate microcapsules as a model for exploring mitochondrial and glycolytic metabolism using the Seahorse XFe24 Analyzer.

Author

Ghiraldelli Miranda, Raul, Machado, Ivo F., Rolo, Anabela Pinto, Dorta, Daniel Junqueira, and Palmeira, Carlos Manuel Marques

Subjects
*ANIMAL culture, *ANIMAL experimentation, *GLUCOSE metabolism, *OXIDATIVE phosphorylation, *ALGINIC acid
Abstract

Abstract\nHIGHLIGHTSMitochondria are affected by chemical substances and play a critical role in drug-induced liver injury (DILI). Chemical substances can have a significant impact on various cellular processes, such as the disruption of oxidative phosphorylation, oxidative stress, and alteration of glucose metabolism. Given the consequences of these effects, it is crucial to understand the molecular pathways of chemical substances in the context of hepatotoxicity to prevent and treat DILI. In this regard, the Seahorse XFe24 Analyzer is a valuable tool for assessing mitochondrial bioenergetics and glucose metabolism. The Mito Stress Test and Glycolytic Rate Assay allow real-time assessment of the metabolic state after chemical exposure. Additionally, HepG2 spheroids have emerged as an important alternative tool for assessing hepatotoxicity, as they provide results that are more comparable to those found in humans than monolayer cultures or animal tests (such as rodent tests). By integrating these two powerful tools, it is possible to bridge the gap between animal and human tests, resulting in more reliable results in the assessment of human hepatotoxicity and DILI. However, because of the high variability in characteristics between 3D cultures (such as spheroids and organoids), XF analyzer assays are not well optimized for use with HepG2 spheroids. Here, we describe a streamlined and optimized protocol for performing the Mito Stress Test and Glycolytic Rate Assay using HepG2 spheroids cultured in alginate microcapsules in the Seahorse XFe24 Analyzer.HepG2 spheroids were formed in alginate microcapsule for 5 days.The Mito Stress Test protocol for multiple HepG2 spheroids is described.The Glycolytic Rate Assay protocol for multiple HepG2 spheroids is described.The Seahorse XFe24 Analyzer assays were normalized by the number of spheroids.HepG2 spheroids were formed in alginate microcapsule for 5 days.The Mito Stress Test protocol for multiple HepG2 spheroids is described.The Glycolytic Rate Assay protocol for multiple HepG2 spheroids is described.The Seahorse XFe24 Analyzer assays were normalized by the number of spheroids. [ABSTRACT FROM AUTHOR]

Published
2025
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21. Mitochondrial respiratory states and rates

Author

Gnaiger, Erich, Aasander Frostner, Eleonor, Abdul Karim, Norwahidah, Abumrad, Nada A, Acuna-Castroviejo, Dario, Adiele, Reginald C, Ahn, Bumsoo, Ali, Sameh S, Alton, Lesley, Alves, Marco G, Amati, Francesca, Amoedo, Nivea Dias, Andreadou, Ioanna, Arago, Marc, Aral, Cenk, Arandarcikaite, Odeta, Armand, Anne-Sophie, Arnould, Thierry, Avram, Vlad Florian, Bailey, Damian M, Bajpeyi, Sudip, Bajzikova, Martina, Bakker, Barbara M, Barlow, Jonathan, Bastos Sant'Anna Silva, Ana Carolina, Batterson, Philip, Battino, Maurizio, Bazil, Jason, Beard, Daniel A, Bednarczyk, Piotr, Bello, Fiona, Ben-Shachar, Dorit, Bergdahl, Andreas, Berge, Rolf K, Bergmeister, Lisa, Bernardi, Paolo, Berridge, Michael V, Bettinazzi, Stefano, Bishop, David, Blier, Pierre U, Blindheim, Dan Filip, Boardman, Neoma T, Boetker, Hans Erik, Borchard, Sabine, Boros, Mihaly, Borsheim, Elisabet, Borutaite, Vilma, Botella, Javier, Bouillaud, Frederic, Bouitbir, Jamal, Boushel, Robert C, Bovard, Josh, Breton, Sophie, Brown, David A, Brown, Guy C, Brown, Robert A, Brozinick, Joseph T, Buettner, Garry R, Burtscher, Johannes, Calabria, Elisa, Calbet, Jose A, Calzia, Enrico, Cannon, Daniel T, Cano Sanchez, Maria, Canto Alvarez, Carlos, Cardoso, Luiza Helena Daltro, Carvalho, Eugenia, Casado Pinna, Marta, Cassar, Samantha, Cassina, Adriana M, Castelo, Maria P, Gonzalez-Franquesa, A, Cavalcanti-de-Albuquerque, Joao Paulo, Cervinkova, Zuzana, Chabi, Beatrice, Chakrabarti, Lisa, Chakrabarti, Sasanka, Chaurasia, Bhagirath, Chen, Qi, Chicco, Adam J, Chinopoulos, Christos, Chowdhury, Subir K, Cizmarova, Beata, Clementi, Emilio, Coen, Paul M, Cohen, Bruce H, Coker, Robert H, Collin, Anne, Crisostomo, Luis, Dahdah, Norma, Dalgaard, Louise T, Dambrova, Maija, Danhelovska, Tereza, Darveau, Charles A, Das, Anibh M, Dash, Ranjan K, Davidova, Eliska, Davis, Michael S, De Goede, Paul, De Palma, Clara, Dembinska-Kiec, Aldona, Detraux, Damien, Devaux, Yvan, Di Marcello, Marco, Dias, Tania R, Distefano, Giovanna, Doermann, Niklas, Doerrier, Carolina, Dong, Lan-Feng, Donnelly, Chris, Drahota, Zdenek, Duarte, Filipe Valente, Dubouchaud, Herve, Duchen, Michael R, Dumas, Jean-Francois, Durham, William J, Dymkowska, Dorota, Dyrstad, Sissel E, Dyson, Alex, Dzialowski, Edward M, Eaton, Simon, Ehinger, Johannes, Elmer, Eskil, Endlicher, Rene, Engin, Ayse B, Escames, Germaine, Ezrova, Zuzana, Falk, Marni Joy, Fell, David A, Ferdinandy, Peter, Ferko, Miroslav, Ferreira, Julio Cesar Batista, Ferreira, Rita, Ferri, Alessandra, Fessel, Joshua P, Filipovska, Aleksandra, Fisar, Zdenek, Fischer, Christine, Fischer, Michael, Fisher, Gordon, Fisher, Joshua J, Ford, Ellen, Fornaro, Mara, Galina, Antonio, Galkin, Alexander, Gallee, Leon, Galli, Gina L, Gama Perez, Pau, Gan, Zhenji, Ganetzky, Rebecca, Garcia-Rivas, Gerardo, Garcia-Roves, Pablo Miguel, Garcia-Souza, Luiz Felipe, Garipi, Enis, Garlid, Keith D, Garrabou, Gloria, Garten, Antje, Gastaldelli, Amalia, Gayen, Jiaur, Genders, Amanda J, Genova, Maria Luisa, Giovarelli, Matteo, Goncalo Teixeira da Silva, Rui, Goncalves, Debora Farina, Gonzalez-Armenta, Jenny L, Gonzalez-Freire, Marta, Gonzalo, Hugo, Goodpaster, Bret H, Gorr, Thomas A, Gourlay, Campbell W, Granata, Cesare, Grefte, Sander, Guarch, Meritxell Espino, Gueguen, Naig, Gumeni, Sentiljana, Haas, Clarissa B, Haavik, Jan, Haendeler, Judith, Haider, Markus, Hamann, Andrea, Han, Jin, Han, Woo Hyun, Hancock, Chad R, Hand, Steven C, Handl, Jiri, Hargreaves, Ian P, Harper, Mary Ellen, Harrison, David K, Hassan, Hazirah, Hausenloy, Derek J, Heales, Simon JR, Heiestad, Christina, Hellgren, Kim T, Hepple, Russell T, Hernansanz-Agustin, Pablo, Hewakapuge, Sudinna, Hickey, Anthony J, Ho, Dieu Hien, Hoehn, Kyle L, Hoel, Frederik, Holland, Olivia J, Holloway, Graham P, Hoppel, Charles L, Hoppel, Florian, Houstek, Josef, Huete-Ortega, Maria, Hyrossova, Petra, Iglesias-Gonzalez, Javier, Irving, Brian A, Isola, Raffaella, Iyer, Shilpa, Jackson, Christophe B, Jadiya, Pooja, Jana, Prado Fabian, Jang, David H, Jang, Young C, Janowska, Joanna, Jansen, Kirsten, Jansen-Duerr, Pidder, Jansone, Baiba, Jarmuszkiewicz, Wieslawa, Jaskiewicz, Anna, Jedlicka, Jan, Jespersen, Nichlas R, Jha, Rajan K, Jurczak, Michael J, Jurk, Diana, Kaambre, Tuuli, Kaczor, Jan J, Kainulainen, Heikki, Kampa, Rafal Pawel, Kandel, Sunil M, Kane, Daniel A, Kapferer, Werner, Kappler, Lisa, Karabatsiakis, Alexander, Karkucinska-Wieckowska, Agnieszka, Kaur, Sarbjot, Keijer, Jaap, Keller, Markus A, Keppner, Gloria, Khamoui, Andy V, Kidere, Dita, Kilbaugh, Todd, Kim, Hyoung Kyu, Kim, Julian KS, Klepinin, Aleksandr, Klepinina, Lyudmila, Klingenspor, Martin, Klocker, Helmut, Komlódi, Timea, Koopman, Werner JH, Kopitar-Jerala, Natasa, Kowaltowski, Alicia J, Kozlov, Andrey V, Krajcova, Adela, Krako Jakovljevic, Nina, Kristal, Bruce S, Krycer, Jamer R, Kuang, Jujiao, Kucera, Otto, Kuka, Janis, Kwak, Hyo Bum, Kwast, Kurt, Laasmaa, Martin, Labieniec-Watala, Magdalena, Lai, Nicola, Land, John M, Lane, Nick, Laner, Verena, Lanza, Ian R, Larsen, Terje S, Lavery, Gareth G, Lazou, Antigone, Lee, Hong Kyu, Leeuwenburgh, Christiaan, Lehti, Maarit, Lemieux, Helene, Lenaz, Giorgio, Lerfall, Jorgen, Li, Pingan A, Li Puma, Lance, Liepins, Edgars, Lionett, Sofie, Liu, Jiankang, Lopez, Luis C, Lucchinetti, Eliana, Ma, Tao, Macedo, Maria P, Maciej, Sarah, MacMillan-Crow, Lee Ann, Majtnerova, Pavlina, Makarova, Elina, Makrecka-Kuka, Marina, Malik, Afshan N, Markova, Michaela, Martin, Daniel S, Martins, Ana Dias, Martins, Joao D, Maseko, Tumisang Edward, Maull, Felicia, Mazat, Jean Pierre, McKenna, Helen T, McKenzie, Matthew, Menze, Michael A, Merz, Tamara, Meszaros, Andras T, Methner, Axel, Michalak, Slawomir, Moellering, Douglas R, Moisoi, Nicoleta, Molina, Anthony JA, Montaigne, David, Moore, Anthony L, Moreau, Kerrie, Moreira, Bruno P, Moreno-Sanchez, Rafael, Mracek, Tomas, Muccini, Anna Maria, Muntane, Jordi, Muntean, Danina M, Murray, Andrew J, Musiol, Eva, Nabben, Miranda, Nair, K Sreekumaran, Nehlin, Jan O, Nemec, Michal, Neufer, P Darrell, Neuzil, Jiri, Neviere, Remi, Newsom, Sean A., Nozickova, Katerina, O'Brien, Katie A, O'Gorman, Donal, Olgar, Yusuf, Oliveira, Ben, Oliveira, Marcus F, Oliveira, Marcos Tulio, Oliveira, Pedro F, Oliveira, Paulo J, Orynbayeva, Zulfiya, Osiewacz, Heinz D, Pak, Youngmi K, Pallotta, Maria L, Palmeira, Carlos M, Parajuli, Nirmala, Passos, Joao F, Passrugger, Manuela, Patel, Hemal H, Pavlova, Nadia, Pecina, Petr, Pedersen, Tina M, Pereira da Silva Grilo da Silva, Filomena, Perez Valencia, Juan A, Perks, Kara L, Pesta, Dominik, Petit, Patrice X, Pettersen, Ina Katrine Nitschke, Pichaud, Nicolas, Pichler, Irene, Piel, Sarah, Pietka, Terri A, Pino, Maria F, Pirkmajer, Sergej, Plangger, Mario, Porter, Craig, Porter, Richard K, Procaccio, Vincent, Prochownik, Edward V, Prola, Alexandre, Pulinilkunnil, Thomas, Puskarich, Michael A, Puurand, Marju, Radenkovic, Filip, Ramzan, Rabia, Rattan, Suresh IS, Reboredo, Patricia, Renner-Sattler, Kathrin, Rial, Eduardo, Robinson, Matthew M, Roden, Michael, Rodriguez, Enrique, Rodriguez-Enriquez, Sara, Roesland, Gro Vatne, Rohlena, Jakub, Rolo, Anabela Pinto, Ropelle, Eduardo R, Rossignol, Rodrigue, Rossiter, Harry B, Rubelj, Ivica, Rybacka-Mossakowska, Joanna, Saada, Ann, Safaei, Zahra, Sarlak, S, Salin, Karine, Salvadego, Desy, Sandi, Carmen, Saner, Nicholas, Sanz, Alberto, Sazanov, Leonid A, Scatena, Roberto, Schartner, Melanie, Scheibye-Knudsen, Morten, Schilling, Jan M, Schlattner, Uwe, Schoenfeld, Peter, Schots, Pauke C, Schulz, Rainer, Schwarzer, Christoph, Scott, Graham R, Selman, Colin, Shabalina, Irina G, Sharma, Pushpa, Sharma, Vipin, Shevchuk, Igor, Shirazi, Reza, Shiroma, Jonathan G, Siewiera, Karolina, Silber, Ariel M, Silva, Ana Maria, Sims, Carrie A, Singer, Dominique, Singh, Brijesh Kumar, Skolik, Robert A, Smenes, Benedikte Therese, Smith, James, Soares, Félix Alexandre Antunes, Sobotka, Ondrej, Sokolova, Inna, Sonkar, Vijay K, Sowton, Alice P, Sparagna, Genevieve C, Sparks, Lauren M, Spinazzi, Marco, Stankova, Pavla, Starr, Jonathan, Stary, Creed, Stelfa, Gundega, Stepto, Nigel K, Stiban, Johnny, Stier, Antoine, Stocker, Roland, Storder, Julie, Sumbalova, Zuzana, Suomalainen, Wartiovaara Anu, Suravajhala, Prashanth, Svalbe, Baiba, Swerdlow, Russel H, Swiniuch, Daria, Szabo, Ildiko, Szewczyk, Adam, Szibor, Marten, Tanaka, Masashi, Tandler, Bernard, Tarnopolsky, Mark A, Tausan, Daniel, Tavernarakis, Nektarios, Tepp, Kersti, Thakkar, Himani, Thapa, Maheshwo, Thyfault, John P, Tomar, Dhanendra, Ton, Riccardo, Torp, May-Kristin, Towheed, Atif, Tretter, Laszlo, Trewin, Adam J, Trifunovic, Aleksandra, Trivigno, Catherine, Tronstad, Karl Johan, Trougakos, Ioannis P, Truu, Laura, Tuncay, Erkan, Turan, Belma, Tyrrell, Daniel J, Urban, Tomas, Valentine, Joseph Marco, Van Bergen, Nicole J, Van Hove, Johan, Varricchio, Frederick, Vella, Joanna, Vendelin, Marko, Vercesi, Anibal E, Victor, Victor Manuel, Vieira Ligo Teixeira, Camila, Vidimce, Josif, Viel, Christian, Vieyra, Adalberto, Vilks, Karlis, Villena, Joseph A, Vincent, Vinnyfred, Vinogradov, Andrey D, Viscomi, Carlo, Vitorino, Rui Miguel Pinheiro, Vogt, Sebastian, Volani, Chiara, Volska, Kristine, Votion, Dominique-Marie, Vujacic-Mirski, Ksenija, Wagner, Brett A, Ward, Marie Louise, Warnsmann, Verena, Wasserman, David H, Watala, Cezary, Wei, Yau-Huei, Whitfield, Jamie, Wickert, Anika, Wieckowski, Mariusz R, Wiesner, Rudolf J, Williams, Caroline M, Winwood-Smith, Hugh, Wohlgemuth, Stephanie E, Wohlwend, Martin, Wolff, Jonci Nikolai, Wrutniak-Cabello, Chantal, Wuest, Rob C I, Yokota, Takashi, Zablocki, Krzysztof, Zanon, Alessandra, Zanou, Nadege, Zaugg, Kathrin, Zaugg, Michael, Zdrazilova, Lucie, Zhang, Yong, Zhang, Yi Zhu, Zikova, Alena, Zischka, Hans, Zorzano, Antonio, Zvejniece, Liga, Lagarrigue, Sylviane, Munro, Daniel, Pereira, Susana, Laranjinha, Joäo, Almeida, Angeles, Diederich, M, Hecker, M, Jusic, A, Prigione, A, Sommer, N, Weissig, V, Abdel-Rahman, EA, Sova, M, Amorim, R, Beleza, J, Bravo-Sagua, R, Celen, MC, Coxito, P, Crispim, M, Dias, C, Evinova, A, Fuertes Agudo, M, Gao, Y, Garcia, G, Goikoetxea Usandizaga, N, Grilo, L, Minuzzi, LM, Hachmo, Y, Hajrulahovic, A, Hatokova, Z, Henrique, A, Holzner, L, Kimoloi, S, Ledo, AM, Machado, IF, Magalhaes, J, Magri, A, Nunes, S, Oliveira, J, Pinho, SA, Preguica, I, Reano, S, Rodrigues, AS, Santos, D, Sardao, V, Stevanovic, J, Teodoro, J, Van der Ende, M, Zujovic, T, Djafarzadeh, S, Schneider Gasser, EM, Jaspers, RT, Arias-Reyes, C, Bairam, A, Laouafa, S, Marcouiller, F, Soliz, J, Glatz, J, Antunes, D, Bach de Courtade, SM, Bardal, T, Di Paola, FJ, Fulton, M, Grams, B, Joseph, V, Kwon, OS, Liang, L, Mila Guasch, M, Moore, C, Norman, J, O'Brien, K, Olsen, RE, Paez, H, Rees, BB, Roshanravan, B, Scaife, P, Sendon, PM, Vlachaki Walker, J, Crossland, H, Jones, JG, Bento, G, Perales, JC, and Aragones Lopez, J

Subjects
uncoupling, Mitochondrial respiratory control, coupling control, protonmotive force, oxidative phosphorylation, mitochondrial respiratory control, NARILIS, ET [electron transfer], electron transfer, residual oxygen consumption, flux, normalization, efficiency, flow, oxygen, mitochondrial preparations, proton leak
Abstract

As the knowledge base and importance of mitochondrial physiology to human health expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow guidelines of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of databases of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery.

Published
2019
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26. Aldehyde Dehydrogenase 2 (ALDH2) in Rat Fatty Liver Cold Ischemia Injury

Author

Instituto de Salud Carlos III, European Commission, Panisello-Roselló, Arnau, Alva, Norma, Flores, Marta, López, Alexandre, Castro-Benítez, Carlos, Folch-Puy, Emma, Rolo, Anabela Pinto, Palmeira, Carlos M., Adam, René, Carbonell, Teresa, Roselló-Catafau, Joan, Instituto de Salud Carlos III, European Commission, Panisello-Roselló, Arnau, Alva, Norma, Flores, Marta, López, Alexandre, Castro-Benítez, Carlos, Folch-Puy, Emma, Rolo, Anabela Pinto, Palmeira, Carlos M., Adam, René, Carbonell, Teresa, and Roselló-Catafau, Joan

Abstract

Institut George Lopez-1 (IGL-1) and Histidine-tryptophan-ketoglutarate (HTK) solutions are proposed as alternatives to UW (gold standard) in liver preservation. Their composition differs in terms of the presence/absence of oncotic agents such as HES or PEG, and is decisive for graft conservation before transplantation. This is especially so when fatty (steatotic) livers are used since these grafts are more vulnerable to ischemia insult during conservation. Their composition determines the extent of the subsequent reperfusion injury after transplantation. Aldehyde dehydrogenase-2 (ALDH2), a mitochondrial enzyme, has been reported to play a protective role in warm ischemia-reperfusion injury (IRI), but its potential in fatty liver cold ischemic injury has not yet been investigated. We evaluated the relevance of ALDH2 activity in cold ischemia injury when fatty liver grafts from Zucker Obese rats were preserved in UW, HTK, and IGL-1 solutions, in order to study the mechanisms involved. ALDH2 upregulation was highest in livers preserved in IGL-1. It was accompanied by a decrease in transaminases, apoptosis (Caspase 3 and TUNEL assay), and lipoperoxidation, which was concomitant with the effective clearance of toxic aldehydes such as 4-hydroxy-nonenal. Variations in ATP levels were also determined. The results were consistent with levels of NF-E2 p45-related factor 2 (Nrf2), an antioxidant factor. Here we report for the first time the relevance of mitochondrial ALDH2 in fatty liver cold preservation and suggest that ALDH2 could be considered a potential therapeutic target or regulator in clinical transplantation.

Published
2018

32. Indirubin and NAD+ prevent mitochondrial ischaemia/reperfusion damage in fatty livers.

Author

Teodoro, João Soeiro, Varela, Ana Teresa, Duarte, Filipe Valente, Gomes, Ana Patrícia, Palmeira, Carlos Marques, and Rolo, Anabela Pinto

Subjects
INDIRUBIN, FATTY liver, ISCHEMIA, REPERFUSION injury, MITOCHONDRIAL pathology, PREVENTION
Abstract

Abstract: Background: Fatty livers are considerably more susceptible to acute stressors, such as ischaemia/reperfusion (I/R). As the incidence of I/R is high due to surgical events and some pathologies, there is an urgent need to find strategies against I/R injury (I/RI) in fatty livers. We postulate that an acute pretreatment with indirubin‐3′‐oxime (Ind) or NAD+ prevents mitochondrial dysfunction associated with warm I/RI in fatty livers. Materials and Methods: Zucker fatty rats were subjected to warm ischaemia and 12 hours of reperfusion. Ind or NAD+ was administered in the hepatic artery 30 minutes before ischaemia. Hepatic mitochondrial isolation was performed, and functional assays as well as molecular analysis were performed. Results: Pretreatment decreased markers of liver injury while preserving mitochondrial cytochrome c content, which is related to the prevention of calcium‐induced mitochondrial permeability transition (mPT), the decline in mitochondrial respiratory state 3 and ATP content. The generation of reactive oxygen species (ROS) was also diminished. Inhibition of GSK‐3ß by Ind resulted in the prevention of cyclophilin‐D (CypD) phosphorylation, unabling it to bind to the adenine nucleotide translocator (ANT), thus, preventing mPT induction. Furthermore, deacetylation of CypD at Lys residue by sirtuin 3 (SIRT3) caused its dissociation from ANT, contributing to an increase in mPT threshold in NAD+‐pretreated animals. Conclusions: Pretreatment with Ind or NAD+ protects fatty livers by maintaining mitochondrial calcium homoeostasis, thus, preserving mitochondrial function and energetic balance. As such, CypD might be a new protective target against I/RI in fatty livers. [ABSTRACT FROM AUTHOR]

Published
2018
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33. Sirtuin 1 in rat orthotopic liver transplantation: An IGL-1 preservation solution approach

Author

Pantazi, Eirini, Zaouali, Mohamed A., Bejaoui, Mohamed, Folch-Puy, Emma, Abdennebi, Hassen B., Varela, Ana Teresa, Rolo, Anabela Pinto, Palmeira, Carlos M., Roselló-Catafau, Joan, Pantazi, Eirini, Zaouali, Mohamed A., Bejaoui, Mohamed, Folch-Puy, Emma, Abdennebi, Hassen B., Varela, Ana Teresa, Rolo, Anabela Pinto, Palmeira, Carlos M., and Roselló-Catafau, Joan

Abstract

© The Author(s) 2015. AIM: To investigate the possible involvement of Sirtuin 1 (SIRT1) in rat orthotopic liver transplantation (OLT), when Institute Georges Lopez 1 (IGL-1) preservation solution is enriched with trimetazidine (TMZ). METHODS: Male Sprague-Dawley rats were used as donors and recipients. Livers were stored in IGL-1 preservation solution for 8h at 4 °C, and then underwent OLT according to Kamada's cuff technique without arterialization. In another group, livers were stored in IGL-1 preservation solution supplemented with TMZ, at 10-6 mol/L, for 8 h at 4 °C and then underwent OLT. Rats were sacrificed 24 h after reperfusion, and liver and plasma samples were collected. Liver injury (transaminase levels), mitochondrial damage (glutamate dehydrogenase activity) oxidative stress (malondialdehyde levels), and nicotinamide adenine dinucleotide (NAD+), the co-factor necessary for SIRT1 activity, were determined by biochemical methods. SIRT1 and its substrates (ac-FoxO1, ac-p53), the precursor of NAD+, nicotinamide phosphoribosyltransferase (NAMPT), as well as the phosphorylation of adenosine monophosphate activated protein kinase (AMPK), p-mTOR, p-p70S6K (direct substrate of mTOR), autophagy parameters (beclin-1, LC3B) and MAP kinases (p-p38 and p-ERK) were determined by Western blot. RESULTS: Liver grafts preserved in IGL-1 solution enriched with TMZ presented reduced liver injury and mitochondrial damage compared with those preserved in IGL-1 solution alone. In addition, livers preserved in IGL-1 + TMZ presented reduced levels of oxidative stress. This was consistent with enhanced SIRT1 protein expression and elevated SIRT1 activity, as indicated by decreased acetylation of p53 and FoxO1. The elevated SIRT1 activity in presence of TMZ can be attributed to the enhanced NAMPT protein and NAD+/NADH levels. Up-regulation of SIRT1 was consistent with activation of AMPK and inhibition of phosphorylation of mTOR and its direct substrate (p-p70S6K). As a consequenc

Published
2015

36. The bile acid chenodeoxycholic acid directly modulates metabolic pathways in white adipose tissue in vitro: insight into how bile acids decrease obesity.

Author

Teodoro, João Soeiro, Rolo, Anabela Pinto, Jarak, Ivana, Palmeira, Carlos Marques, and Carvalho, Rui Albuquerque

Abstract

Obesity is a worldwide epidemic, and associated pathologies, including type 2 diabetes and cardiovascular alterations, are increasingly escalating morbidity and mortality. Despite intensive study, no effective simple treatment for these conditions exists. As such, the need for go-to drugs is serious. Bile acids (BAs) present the possibility of reversing these problems, as various in vivo studies and clinical trials have shown significant effects with regard to weight and obesity reduction, insulin sensitivity restoration and cardiovascular improvements. However, the mechanism of action of BA-induced metabolic improvement has yet to be fully established. The currently most accepted model involves non-shivering thermogenesis for energy waste, but this is disputed. As such, we propose to determine whether the BA chenodeoxycholic acid (CDCA) can exert anti-obesogenic effects in vitro, independent of thermogenic brown adipose tissue activation. By exposing differentiated 3 T3-L1 adipocytes to high glucose and CDCA, we demonstrate that this BA has anti-obesity effects in vitro. Nuclear magnetic resonance spectroscopic analysis of metabolic pathways clearly indicates an improvement in metabolic status, as these cells become more oxidative rather than glycolytic, which may be associated with an increase in fatty acid oxidation. Our work demonstrates that CDCA-induced metabolic alterations occur in white and brown adipocytes and are not totally dependent on endocrine/nervous system signaling, as thought until now. Furthermore, future exploration of the mechanisms behind these effects will undoubtedly reveal interesting targets for clinical modulation. [ABSTRACT FROM AUTHOR]

Published
2016
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39. PPARα Agonist WY-14643 Induces SIRT1 Activity in Rat Fatty Liver Ischemia-Reperfusion Injury.

Author

Pantazi, Eirini, Folch-Puy, Emma, Bejaoui, Mohamed, Panisello, Arnau, Varela, Ana Teresa, Rolo, Anabela Pinto, Palmeira, Carlos Marques, and Roselló-Catafau, Joan

Subjects
ISCHEMIA, REPERFUSION injury, METABOLISM, PEROXISOME proliferator-activated receptors, DEACETYLASES, SIRTUINS, ENDOPLASMIC reticulum, FATTY liver
Abstract

Ischemia-reperfusion injury (IRI) remains a frequent complication in surgery, especially in case of steatotic livers that present decreased tolerance towards IRI. Apart from its major role in metabolism, activation of peroxisome proliferator-activated receptor α (PPARα) has been related with positive effects on IRI. In addition, the deacetylase enzyme sirtuin 1 (SIRT1) has recently emerged as a promising target for preventing IRI, through its interaction with stress-related mechanisms, such as endoplasmic reticulum stress (ERS). Taking this into account, this study aims to explore whether PPARα agonist WY-14643 could protect steatotic livers against IRI through sirtuins and ERS signaling pathway. Obese Zucker rats were pretreated or not pretreated with WY-14643 (10 mg/kg intravenously) and then submitted to partial (70%) hepatic ischemia (1 hour) followed by 24 hours of reperfusion. Liver injury (ALT levels), lipid peroxidation (MDA), SIRT1 activity, and the protein expression of SIRT1 and SIRT3 and ERS parameters (IRE1α, peIF2, caspase 12, and CHOP) were evaluated. Treatment with WY-14643 reduced liver injury in fatty livers, enhanced SIRT1 activity, and prevented ERS. Together, our results indicated that PPARα agonist WY-14643 may exert its protective effect in fatty livers, at least in part, via SIRT1 induction and ERS prevention. [ABSTRACT FROM AUTHOR]

Published
2015
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41. Role of aldehyde dehydrogenase 2 in ischemia reperfusion injury: An update

Author

Emma Folch-Puy, Marc Net, Alexandre Lopez, Teresa Carbonell, René Adam, Arnau Panisello-Roselló, Joan Roselló-Catafau, Anabela P. Rolo, Carlos M. Palmeira, Instituto de Salud Carlos III, European Commission, Panisello-Roselló, Arnau, López, Alexandre, Folch-Puy, Emma, Carbonell, Teresa, Rolo, Anabela Pinto, Palmeira, Carlos M., Net, Marc, Roselló-Catafau, Joan, Universitat de Barcelona, Panisello-Roselló, Arnau [0000-0003-2062-6134], López, Alexandre [0000-0001-8978-4486], Folch-Puy, Emma[0000-0002-6277-9027], Carbonell, Teresa [0000-0002-7131-3667], Rolo, Anabela Pinto [0000-0003-3535-9630], Palmeira, Carlos M. [0000-0002-2639-7697], Net, Marc [0000-0003-0906-6404], and Roselló-Catafau, Joan [0000-0001-7127-4883]

Subjects
0301 basic medicine, Aldehyde dehydrogenase, Apoptosis, Pharmacology, medicine.disease_cause, 0302 clinical medicine, Ischemia, Isquèmia, Kidney, biology, Aldehyde Dehydrogenase, Mitochondrial, Gastroenterology, Minireviews, General Medicine, 3. Good health, medicine.anatomical_structure, Liver, Reperfusion Injury, Benzamides, 4-hydroxy-2-nonenal autophagy, Lipid Peroxides, Metabolic Clearance Rate, Enzyme Activators, Preconditioning, 03 medical and health sciences, Diabetes mellitus, medicine, Autophagy, Animals, Humans, Benzodioxoles, ALDH2, Aldehydes, business.industry, Proteins, Organ Transplantation, medicine.disease, Oxidative Stress, 030104 developmental biology, Aldehyde dehydrogenase 2, biology.protein, business, Reactive Oxygen Species, Reperfusion injury, Proteïnes, 030217 neurology & neurosurgery, Oxidative stress, Ischemia reperfusion injury
Abstract

Aldehyde dehydrogenase 2 (ALDH2) is best known for its critical detoxifying role in liver alcohol metabolism. However, ALDH2 dysfunction is also involved in a wide range of human pathophysiological situations and is associated with complications such as cardiovascular diseases, diabetes mellitus, neurodegenerative diseases and aging. A growing body of research has shown that ALDH2 provides important protection against oxidative stress and the subsequent loading of toxic aldehydes such as 4-hydroxy-2-nonenal and adducts that occur in human diseases, including ischemia reperfusion injury (IRI). There is increasing evidence of its role in IRI pathophysiology in organs such as heart, brain, small intestine and kidney; however, surprisingly few studies have been carried out in the liver, where ALDH2 is found in abundance. This study reviews the role of ALDH2 in modulating the pathways involved in the pathophysiology of IRI associated with oxidative stress, autophagy and apoptosis. Special emphasis is placed on the role of ALDH2 in different organs, on therapeutic “preconditioning” strategies, and on the use of ALDH2 agonists such as Alda-1, which may become a useful therapeutic tool for preventing the deleterious effects of IRI in organ transplantation., This work was supported by Instituto de Salud Carlos III through FIS project PI 15/00110 co-funded by FEDER from Regional Development European Funds (European Union) and the FOIE GRAS project, which has received funding from the European Union’s Horizon 2020 Research and Innovation programme under the Marie Sklodowska-Curie Grant (Agreement No. 722619).

Published
2018

45. Alteração da sinalização dopaminérgica por desnervação do corpo carotídeo na modulação da função do tecido adiposo na síndrome metabólica

Author

Santos, Ana Sofia Chasqueira dos, Rolo, Anabela Pinto, and Matafome, Paulo Nuno Centeio

Subjects
Síndrome Metabólica, Metabolic Syndrome, Carotid body denervation, Peripheral dopamine, Tecido adiposo, Adipose tissue, Resistência à insulina, Insulin resistance, Desnervação do corpo carotídeo, Dopamina periférica
Abstract

Dissertação de Mestrado em Bioquímica apresentada à Faculdade de Ciências e Tecnologia Introdução e objetivos: A Síndrome metabólica (SM) é caraterizada pelo desenvolvimento de um conjunto de distúrbios metabólicos, podendo desencadear doenças como a obesidade e diabetes Mellitus tipo II (DMTII). O corpo carotídeo é um órgão quimiorrecetor, que tem como função detetar alterações no sangue arterial, sendo recentemente implicado como um potencial “glicosensor” e onde a insulina atua de forma preponderante na resposta a baixas contrações de glicemia. Numa situação de hiperinsulinemia, como se verifica na DMTII, há resistência à insulina periférica nos órgãos sensíveis à sua ação, como no tecido adiposo e desta forma, no corpo carotídeo. No entanto, com a resseção bilateral crónica do nervo do seio carotídeo esta situação parece ser revertida. Desta forma, este trabalho tem como objetivo avaliar as alterações da sinalização dopaminérgica por desnervação do corpo carotídeo na sensibilidade à insulina, armazenamento e metabolismo lipídico no tecido adiposo e perfil glicémico em ratos diabéticos e hiperlipidémicos.Métodos: Foram utilizados ratos Wistar, alimentados com dieta normal (W_SD), e ratos Goto-kakizaki (GK), ratos diabéticos tipo II não hiperlipidémicos, que foram divididos em 4 grupos distintos: GK mantidos com dieta normal (GK_SD); GK hiperlipidémicos, pela indução de uma dieta modificada, rica em gordura e sacarose, (GK_HFD); GK hiperlipidémicos, pela indução de uma dieta modificada, rica em gordura e sacarose, sujeitos à cirurgia de desnervação do corpo carotídeo às 20 semanas de vida (GK_HFD_Dn); e GK hiperlipidémicos, pela indução de uma dieta modificada, rica em gordura e sacarose, sujeitos à cirurgia sham às 20 semanas de vida (GK_HFD_Sh) (n=5-10/grupo). Foram avaliados em jejum, antes do sacrifício, os níveis plasmáticos de glicose, lípidos, insulina e glucagina, avaliada a tolerância à insulina e o índice de insulino-resistência (HOMA), bem como os mecanismos associados à captação e utilização da glicose, de oxidação, síntese e armazenamento de ácidos gordos e de sinalização adrenérgica e dopaminérgica no tecido adiposo epididimal (TAE) por Western Blotting. Resultados: A dieta modificada, enriquecida em gordura e sacarose, levou a um agravamento da resistência à insulina, assim como a um aumento dos níveis plasmáticos da glicose, triglicerídeos e colesterol, em jejum, em relação ao grupo GK_SD. No grupo sujeito à cirurgia de desnervação do corpo carotídeo observou-se uma diminuição da ração ingerida e da ingestão calórica associada, da percentagem de ganho de peso, entre a cirurgia e o sacrifício, concordante com a diminuição dos níveis plasmáticos da glicose, triglicerídeos e colesterol, assim como da melhoria da sensibilidade à insulina. No TAE, houve um aumento dos níveis de AMPK-Thr172, responsável pelo aumento da oxidação lípica, e da expressão de recetores dopaminérgicos D1. Conclusão: Estes resultados sugerem que a cirurgia de desnervação do corpo carotídeo levou uma melhoria do perfil glicémico e da resistência à insulina periférica, na DMTII, levando a um aumento de mecanismos de oxidação de ácidos gordos e da sinalização dopaminérgica no TAE, podendo constituir uma técnica inovadora no combate às doenças metabólicas. Introduction and objectives: Metabolic Syndrome (MS) is characterized by the development a set of metabolic disorders, which can trigger diseases such as obesity and type II diabetes mellitus (TIIDM). The carotid body is a chemoreceptor organ, which function is to detect alterations in the arterial blood, being recently implicated as a potential "glucosensor" and where insulin acts preponderantly in the response to low blood glucose contractions. In a situation of hyperinsulinemia, as it happens in the TIIDM, there is resistance to the peripheral insulin in the sensitive organs to its action as in the adipose tissue and, in this way, in the carotid body. However, with chronic carotid sinus nerve bilateral resections of the carotid body, this situation is reversed. In this way, this work aims to evaluate the alterations of dopaminergic signaling by denervation of the carotid body in insulin sensitivity, storage and lipid metabolism in adipose tissue and glycemic profile in diabetic and hyperlipidemic rats.Methods: Wistar rats fed normal diet (W_SD) and Goto-kakizaki (GK) non-hyperlipidemic type II diabetic rats, were divided into four distinct groups: GK maintained on normal diet (GK_SD); GK hyperlipidemic, by the induction of a modified diet, rich in fat and sucrose, (GK_HFD); GK hyperlipidemic, by the induction of a modified diet, rich in fat and sucrose, subjected to carotid body denervation surgery at 20 weeks of age (GK_HFD_Dn); And hyperlipidemic GK, by induction of a modified diet, high in fat and sucrose, subject to sham surgery at 20 weeks of age (GK_HFD_Sh) (n=5-10/group). Glucose, lipid, insulin and glucagon levels were evaluated before fasting, insulin tolerance and insulin resistance index (HOMA) were evaluated, as well as the mechanisms associated with the uptake and utilization of glucose, oxidation, synthesis and storage of fatty acids and adrenergic and dopaminergic signaling in epididymal adipose tissue (EAT) by Western blotting. Results: The modified diet, enriched in fat and sucrose, led to a worsening of insulin resistance, as well as an increase of fasting levels of glycemia, triglycerides and cholesterol, in relation to the GK_SD group. In the group of carotid body denervation, a decrease in ingested ration and associated caloric intake, the percentage of weight gain between surgery and sacrifice, was observed, in agreement with the decrease in plasma levels of glycemia, triglycerides and cholesterol, as well as improving insulin sensitivity. In EAT, increased levels of AMPK-Thr172, responsible for the increase of lipid oxidation, and expression of dopaminergic D1 receptors were observed.Conclusions: These results suggest that the carotid body denervation surgery led to an improvement in the glycemic profile and peripheral insulin resistance, in the TIIDM, leading to an increase of fatty acid oxidation mechanisms and dopaminergic signaling in TAE, being an innovative technique against metabolic diseases.

Published
2017

48. Role of the sphingomyelinase Isc1p in the regulation of iron homeostasis in Saccharomyces cerevisia

Author

Martins, Telma Filipa da Silva, Pereira, Clara Isabel Ferreira, Rolo, Anabela Pinto, and Pereira, Maria de Lourdes Gomes

Subjects
Sphingolipids, Oxidative stress, Mitocôndrias - Metabolismo, Iron, Isc1p, Aft1p, Stresse oxidativo, Ferrous iron, Leveduras, Metabolismo do ferro, Metaloproteínas, Ferric iron, Biologia molecular
Abstract

Mestrado em Biologia Molecular e Celular Iron is an essential element for cell viability since it is a component of several metalloproteins, containing iron-sulfur clusters and heme centers. The ability to gain and lose electrons, switching between the ferrous (Fe2+) and ferric (Fe3+) states, renders the involvement of iron in many cellular processes. Iron acquisition systems have to be highly regulated to assure a continuous supply of iron but simultaneously prevent its toxicity associated with the formation of hydroxyl radicals by the Fenton reaction. Loss of iron homeostasis is behind many pathologies, highlighting the importance of understanding the mechanisms involved in iron homeostasis. The Saccharomyces cerevisiae inositolphosphosphingolipid phospholipase C (Isc1p) hydrolyses complex sphingolipids to produce ceramide, a bioactive sphingolipid. ISC1 deletion is characterized by premature aging, oxidative stress sensitivity and mitochondrial dysfunction. This mutant also exhibits an up regulation of genes involved in iron uptake leading to increased levels of iron. However the growth phase in which iron accumulation occurs, the specific site of accumulation or even the oxidation state of the accumulated iron in isc1Δ cells remains uncharacterized. Futhermore, the molecular mechanisms behind the iron overload in isc1Δ cells are not known. By monitoring iron levels and oxidation state along growth, it was possible to observe that deletion of ISC1 caused iron accumulation in all phases of growth in both the ferric and ferrous forms. Additionally to the increased iron levels, isc1Δ cells also exhibited an altered distribution of iron within the cell. Unlike wild type, isc1Δ cells did not accumulate ferric iron in the vacuole, but instead, iron seemed to be distributed throughout the cell. Furthermore, iron accumulation in isc1Δ cells was associated with the activation of Aft1p, the low iron-sensing transcriptional activator. Cells lacking Isc1p exhibed higher levels of Aft1p retained in the nucleus, and AFT1 deletion abolished iron accumulation in the isc1Δ mutant. It was also found that dephosphorylation of Aft1p in isc1Δ cells is associated with its activation. Additionally the activation of the phosphatase Sit4p in isc1Δ cells was discarded as a potential mechanism behind Aft1p dephosphorylation and activation, since isc1Δsit4Δ cells still exhibit iron overload. Overall, these results indicate that the dephosphorylation and activation of Aft1p is the factor behind the accumulation of iron in the isc1Δ mutant and reinforce the role of Isc1p in the regulation of iron homeostasis. O Ferro é um elemento essencial para a viabilidade celular, sendo um componente de diversas metaloproteínas, contendo grupos de ferro e enxofre e centros heme. A capacidade de ganhar e perder eletrões, alterando entre os estados ferroso (Fe2+) e férrico (Fe3+), faz com que o ferro esteja envolvido em diversos processos celulares. Os sistemas de aquisição de ferro têm de ser altamente regulados para assegurar um fornecimento contínuo de ferro e simultaneamente prevenir a sua toxicidade associada à formação de radicais hidroxilo pela reação de Fenton. A perda da homeostasia do ferro está associada a muitas patologias, o que enfatiza a importância do estudo dos mecanismos envolvidos na homeostasia do ferro. A proteína inositolfosfoesfingolípido fosfolipase C (Isc1p) presente em Saccharomyces cerevisiae hidrolisa esfingolípidos complexos para produzir ceramida, um esfingolípido bioativo. A deleção do ISC1 é caracterizada pelo envelhecimento celular prematuro, sensibilidade ao stresse oxidativo e disfunção mitocondrial. Este mutante também exibe uma sobreexpressão dos genes envolvidos na captação de ferro, resultando em níveis elevados de ferro. No entanto, a fase do crescimento em que a acumulação do ferro ocorre, o compartimento específico de acumulação ou mesmo o estado de oxidação do ferro acumulado nas células isc1Δ permanece por caracterizar. Além disso, os mecanismos moleculares subjacentes à acumulação de ferro nas células isc1Δ não são conhecidos. Monitorizando os níveis de ferro e o estado de oxidação ao longo do crescimento, foi possível observar que a deleção do ISC1 causou uma acumulação de ferro em todas as fases de crescimento em ambas as formas ferrosa e férrica. Além dos níveis de ferro elevados, as células isc1Δ também exibiram uma alteração na distribuição de ferro no interior da célula. Ao contrário das células wt, as células isc1Δ não acumularam ferro férrico no vacúolo, mas em vez disso, o ferro pareceu estar distribuído por toda a célula. Adicionalmente, a acumulação de ferro nas células isc1Δ foi associada à ativação do Aft1p, o ativador transcricional sensível a níveis baixos de ferro. Células sem a proteína Isc1p exibiram níveis mais elevados de Aft1p retido no núcleo e a delecção do AFT1 suprimiu a acumulação de ferro observada no mutante isc1Δ. Também se observou que a defosforilação do Aft1p nas células isc1Δ está associada à sua ativação. Adicionalmente, a ativação da fosfatase Sit4p nas células isc1Δ como um potencial mecanismo responsável pela defosforilação e ativação do Aft1p foi descartada, uma vez que as células isc1Δsit4Δ continuam a apresentar acumulação de ferro. Em conclusão, estes resultados indicam que a defosforilação e ativação do Aft1p é o fator responsável pela acumulação de ferro no mutante isc1Δ e reforça o papel do Isc1p na regulação da homeostasia do ferro.

Published
2015

49. O papel da esfingomielinase Isc1p na regulação da homeostasia do ferro em Saccharomyces cerevisiae

Author

Martins, Telma Filipa da Silva, Pereira, Clara Isabel Ferreira, Rolo, Anabela Pinto, and Pereira, Maria de Lourdes Gomes

Subjects
Sphingolipids, Oxidative stress, Mitocôndrias - Metabolismo, Iron, Isc1p, Aft1p, Stresse oxidativo, Ferrous iron, Leveduras, Metabolismo do ferro, Metaloproteínas, Ferric iron, Biologia molecular
Abstract

Mestrado em Biologia Molecular e Celular Submitted by Alexandra Bastos (alexandrabastos@ua.pt) on 2016-04-15T17:46:48Z No. of bitstreams: 1 tese.pdf: 2359543 bytes, checksum: ecd8a6d32bce02730fc58a2a0a528b75 (MD5) Made available in DSpace on 2016-04-15T17:46:48Z (GMT). No. of bitstreams: 1 tese.pdf: 2359543 bytes, checksum: ecd8a6d32bce02730fc58a2a0a528b75 (MD5) Previous issue date: 2015-12-22

Published
2015

50. Caracterização do tecido da cicatriz glial, com foco no ácido hialurónico, após compressão medular em ratinhos

Author

Lopes,Maria José Cardoso, Nicaise,Charles, Rolo,Anabela Pinto, and Pereira,Maria de Lourdes Gomes

Subjects
Neurobiologia molecular, Regeneration, Medula espinal - Lesões, Sistema nervoso central - Regeneração, Spinal cord compression, Glial Scar, Hyaluronan, Biologia molecular, Extracellular Matrix
Abstract

Mestrado em Biologia Molecular e Celular Spinal cord injury (SCI) is a devastating neurological disorder that affects thousands of people each year. Although in recent decades significant progress has been made in relation to understanding the molecular and cellular events underlying the nervous damage, spinal cord injury is still a highly disabling condition for which there is no curative therapy. People affected by spinal cord injuries manifested dysfunction or loss, temporary or permanent, of motor, sensory and / or autonomic functions depending on the spinal lesion damaged. Currently, the incidence rate of this type of injury is approximately 15-40 cases per million people worldwide. At the origin of these lesions are: road accidents, falls, interpersonal violence and the practice of sports. In this work we placed the hypothesis that HA is one of the component of the scar tissue formed after a compressive SCI, that it is likely synthetised by the perilesional glial cells and that it might support the permeation of the glial scar during the late phase of SCI. Nowadays, much focus is drawn on the recovery of CNS function, made impossible after SCI due to the high content of sulfated proteoglycans in the extracellular matrix. Counterbalancing the ratio between these proteoglycans and hyaluronic acid could be one of the experimental therapy to re-permeate the glial scar tissue formed after SCI, making possible axonal regrowth and functional recovery. Therefore, we established a model of spinal cord compression in mice and studied the glial scar tissue, particularly through the characterization of the expression of enzymes related to the metabolism of HA and the subsequent concentration thereof at different distances of the lesion epicenter. Our results show that the lesion induced in mice shows results similar to those produced in human lesions, in terms of histologic similarities and behavioral results. but these animals demonstrate an impressive spontaneous reorganization mechanism of the spinal cord tissue that occurs after injury and allows for partial recovery of the functions of the CNS. As regards the study of the glial scar, changes were recorded at the level of mRNA expression of enzymes metabolizing HA i.e., after injury there was a decreased expression of HA synthases 1-2 (HAS 1-2) and an increase of the expression HAS3 synthase mRNA, as well as the enzymes responsible for the HA catabolism, HYAL 1-2. But the amount of HA measured through the ELISA test was found unchanged after injury, it is not possible to explain this fact only with the change of expression of enzymes. At two weeks and in response to SCI, we found synthesized HA by reactive astrocytes and probably by others like microglial cells as it was advanced by the HA/GFAP+ and HA/IBA1+ cells co-location. A lesão medular é uma desordem neurológica devastadora que afeta milhares de pessoas a cada ano. E apesar de nas últimas décadas ter sido feito um enorme progresso relativamente à compreensão dos eventos moleculares e celulares que este dano desencadeia, a lesão medular ainda é uma condição altamente incapacitante e mortal para a qual ainda não há cura. Os indivíduos que apresentam lesões medulares, manifestam disfunção ou perda, temporária ou permanente, das funções motoras, sensoriais e/ou autonómicas. Atualmente a taxa de incidência desta tipologia de lesões é de aproximadamente, 15-40 casos por milhão de pessoas em todo o mundo. Na origem destas lesões estão: acidentes rodoviários, quedas, violência interpessoal e a prática de desportos. Neste trabalho foi colocada a hipótese de que o ácido hialurónico (HA) seja um dos componentes do tecido cicatricial formado após a compressão medular e que provavelmente seja sintetizado pelas células gliais situadas à volta da lesão, podendo ajudar na penetração da cicatriz glial, por parte das células nervosas, durante uma fase mais tardia da lesão da espinal medula. Atualmente tem sido dada muita atenção ao restabelecimento da função do SNC, impossibilitado pelo elevado teor de proteoglicanos sulfatados na matriz extracelular. O contrabalanço do rácio entre o teor de proteoglicanos e de HA pode ser uma terapia experimental para a re-permeabilização do tecido da cicatriz glial formada após a lesão medular, possibilitando o crescimento axonal e a recuperação funcional. Por isso, estabeleceu-se um modelo de compressão da espinal medula em ratinhos e estudou-se o tecido da cicatriz glial, em particular, a caracterização da expressão de enzimas relacionadas com o metabolismo do HA e a sua posterior concentração a diferentes distâncias do epicentro da lesão. Os nossos resultados mostram que a lesão induzida em ratinhos produziu resultados semelhantes às lesões encontradas em humanos, tanto do ponto de vista histológico como funcional. No entanto, após traumatismo, estes animais demonstraram um mecanismo de recuperação espontânea impressionante na espinal medula resultando numa recuperação parcial da função do SNC. Quanto ao estudo da cicatriz glial, as alterações foram detetadas na expressão do mRNA das enzimas metabolizadoras de HA, isto é, após a lesão houve uma diminuição na expressão das HAS1-2 e um aumento na expressão de mRNA da sintase HAS3 assim como das enzimas ligadas à degradação do HA, HYAL 1-2. Porém, duas semanas após LM a concentração de HA medida através do teste ELISA encontrou-se inalterada. É impossível explicar este facto apenas com a mudança na expressão das enzimas ligadas ao HA. A duas semanas pós-trauma, em resposta à LM, encontrámos HA sintetizado por astrócitos reativos e, provavelmente, por outras células, como a microglia tal como foi avançado pela co-localização de HA/IBA1+ e HA/GFAP+. Le traumatisme médullaire est une affection neurologique dévastatrice qui affecte des milliers de personnes chaque année. Bien que ces dernières décennies d'énormes progrès ont été fait par rapport à la compréhension des événements moléculaires et cellulaires qui déclenchent les dommages au sein du tissu nerveux, les dommages de la moelle épinière sont encore irréversibles et rendent les personnes atteintes très invalidées. Aucun traitement visant à remédier aux pertes fonctionnelles n’est disponible. Les gens atteints de traumatismes de la moelle épinière, manifestent un dysfonctionnement ou une perte, temporaire ou permanente, des fonctions motrice, sensorielle et / ou autonome. Actuellement, l’incidence de ce type de blessure est d'environ 15-40 cas par million de personnes dans le monde. L'origine de ces lésions sont: accidents de la route, chutes, violence interpersonnelle et pratique de sports. Dans ce travail, nous avons placé l'hypothèse que l'acide hyaluronique (HA) est l'un des composants du tissu cicatriciel formé après une compression de la moelle épinière, qu'il est probablement synthétisé par les cellules gliales péri lésionnelles et qu'il pourrait soutenir la pénétration de la cicatrice gliale pendant la phase tardive de la LM. Actuellement beaucoup d'attention est attirée sur le rétablissement de la fonction du système SNC, rendue impossible après la LM en raison de la contenu élevé en protéoglycanes sulfatés dans la matrice extracellulaire. Contrebalançant le rapport entre ces protéoglycanes et l'HA peut être une thérapie expérimentale de la re-pénétration dans le tissu de cicatrice gliale formé après la LM, ce qui rend possible le repousse axonale et la récupération fonctionnelle. Par conséquent, nous avons établi un modèle de compression de la moelle épinière chez des souris et étudié le tissu de la cicatrice gliale, en particulier par la caractérisation de l'expression des enzymes liées au métabolisme de l'HA et la concentration ultérieure de celui-ci à des distances différentes de l'épicentre de la lésion. Les résultats montrent que la lésion induite chez la souris produit des résultats similaires à ceux trouvés dans les lésions humaines, d'un point de vue fonctionnel et histologique. Toutefois, après un traumatisme, ces animaux ont démontré un mécanisme de récupération spontanée impressionnante dans la moelle épinière entraînant une reprise partielle de la fonction du système nerveux central. De manière surprenante, la quantité d'HA vérifiée par le test ELISA s’est trouvé inchangée deux semaines après traumatisme médullaire. Il est impossible d'expliquer ce fait uniquement avec le changement de l'expression d'enzymes liées à l'HA. Nous avons constaté que deux semaines après traumatisme, il ya l' HA synthétisé par les astrocytes réactifs et probablement par d'autres comme les cellules microgliales comme il a été avancé par les résultats de colocalisation de l' HA et cellules GFAP+ ainsi que l'HA et cellules IBA1+.

Published
2015

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