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9. Cerebral cystine uptake: a tale of two transporters

Author

McBean, Gethin J.

Subjects
Cystine -- Physiological aspects, Brain -- Physiological aspects, Biological transport -- Research, Biological sciences, Chemistry, Pharmaceuticals and cosmetics industries
Abstract

Transport of cystine across the cell membrane is essential for synthesis of the major cellular antioxidant glutathione. Cystine uptake in the brain occurs by both the [Na.sup.+]-independent [x.sub.c]-cystine--glutamate exchanger and the [X.sub.AG]-family of high-affinity, [Na.sup.+]-dependent glutamate transporters. New evidence concerning the role of cystine transport in the defence against oxidative stress is described.

Published
2002

11. European contribution to the study of ROS:a summary of the findings and prospects for the future from the COST Action BM1203 (EU-ROS)

Author

Egea, Javier, Fabregat, Isabel, Frapart, Yves M., Ghezzi, Pietro, Görlach, Agnes, Kietzmann, Thomas, Kubaichuk, Kateryna, Knaus, Ulla G., Lopez, Manuela G., Olaso-Gonzalez, Gloria, Petry, Andreas, Schulz, Rainer, Vina, Jose, Winyard, Paul, Abbas, Kahina, Ademowo, Stella, Afonso, Catarina B., Andreadou, Ioanna, Antelmann, Haike, Antunes, Fernando, Aslan, Mutay, Bachschmid, Markus M., Barbosa, Rui M., Belousov, Vsevolod, Berndt, Carsten, Bernlohr, David, Bertrán, Esther, Bindoli, Alberto, Bottari, Serge P., Brito, Paula M., Carrara, Guia, Casas, Ana I., Chatzi, Afroditi, Chondrogianni, Niki, Conrad, Marcus, Cooke, Marcus S., Costa, João G., Cuadrado, Antonio, My-Chan Dang, Pham, De Smet, Barbara, Debelec–butuner, Bilge, Dias, Irundika, Dunn, Joe Dan, Edson, Amanda J., El Assar, Mariam, El-Benna, Jamel, Ferdinandy, Péter, Fernandes, Ana S., Fladmark, Kari E., Förstermann, Ulrich, Giniatullin, Rashid, Giricz, Zoltán, Görbe, Anikó, Griffiths, Helen, Hampl, Vaclav, Hanf, Alina, Herget, Jan, Hernansanz-Agustín, Pablo, Hillion, Melanie, Huang, Jinjing, Ilikay, Serap, Jansen-Dürr, Pidder, Jaquet, Vincent, Joles, Jaap A., Kalyanaraman, Balaraman, Kaminskyy, Danylo, Karbaschi, Mahsa, Kleanthous, Marina, Klotz, Lars-Oliver, Korac, Bato, Korkmaz, Kemal Sami, Koziel, Rafal, Kračun, Damir, Krause, Karl-Heinz, Křen, Vladimír, Krieg, Thomas, Laranjinha, João, Lazou, Antigone, Li, Huige, Martínez-Ruiz, Antonio, Matsui, Reiko, Mcbean, Gethin J., Meredith, Stuart P., Messens, Joris, Miguel, Verónica, Mikhed, Yuliya, Milisav, Irina, Milković, Lidija, Miranda-Vizuete, Antonio, Mojović, Milos, Monsalve, María, Mouthuy, Pierre-Alexis, Mulvey, John, Münzel, Thomas, Muzykantov, Vladimir, Nguyen, Isabel T.N., Oelze, Matthias, Oliveira, Nuno G., Palmeira, Carlos M., Papaevgeniou, Nikoletta, Pavićević, Aleksandra, Pedre, Brandán, Peyrot, Fabienne, Phylactides, Marios, Pircalabioru, Gratiela G., Pitt, Andrew R., Poulsen, Henrik E., Prieto, Ignacio, Rigobello, Maria Pia, Robledinos-Antón, Natalia, Rodríguez-mañas, Leocadio, Rolo, Anabela P., Rousset, Francis, Ruskovska, Tatjana, Saraiva, Nuno, Sasson, Shlomo, Schröder, Katrin, Semen, Khrystyna, Seredenina, Tamara, Shakirzyanova, Anastasia, Smith, Geoffrey L., Soldati, Thierry, Sousa, Bebiana C., Spickett, Corinne M., Stancic, Ana, Stasia, Marie José, Steinbrenner, Holger, Stepanić, Višnja, Steven, Sebastian, Tokatlidis, Kostas, Tuncay, Erkan, Turan, Belma, Ursini, Fulvio, Vacek, Jan, Vajnerova, Olga, Valentová, Kateřina, van Breusegem, Frank, Varisli, Lokman, Veal, Elizabeth A., Yalçın, A. Suha, Yelisyeyeva, Olha, Žarković, Neven, Zatloukalová, Martina, Zielonka, Jacek, Touyz, Rhian M., Papapetropoulos, Andreas, Grune, Tilman, Lamas, Santiago, Schmidt, Harald H.H.W., di Lisa, Fabio, Daiber, Andreas, Egea, Javier, Fabregat, Isabel, Frapart, Yves M., Ghezzi, Pietro, Görlach, Agnes, Kietzmann, Thomas, Kubaichuk, Kateryna, Knaus, Ulla G., Lopez, Manuela G., Olaso-Gonzalez, Gloria, Petry, Andreas, Schulz, Rainer, Vina, Jose, Winyard, Paul, Abbas, Kahina, Ademowo, Stella, Afonso, Catarina B., Andreadou, Ioanna, Antelmann, Haike, Antunes, Fernando, Aslan, Mutay, Bachschmid, Markus M., Barbosa, Rui M., Belousov, Vsevolod, Berndt, Carsten, Bernlohr, David, Bertrán, Esther, Bindoli, Alberto, Bottari, Serge P., Brito, Paula M., Carrara, Guia, Casas, Ana I., Chatzi, Afroditi, Chondrogianni, Niki, Conrad, Marcus, Cooke, Marcus S., Costa, João G., Cuadrado, Antonio, My-Chan Dang, Pham, De Smet, Barbara, Debelec–butuner, Bilge, Dias, Irundika, Dunn, Joe Dan, Edson, Amanda J., El Assar, Mariam, El-Benna, Jamel, Ferdinandy, Péter, Fernandes, Ana S., Fladmark, Kari E., Förstermann, Ulrich, Giniatullin, Rashid, Giricz, Zoltán, Görbe, Anikó, Griffiths, Helen, Hampl, Vaclav, Hanf, Alina, Herget, Jan, Hernansanz-Agustín, Pablo, Hillion, Melanie, Huang, Jinjing, Ilikay, Serap, Jansen-Dürr, Pidder, Jaquet, Vincent, Joles, Jaap A., Kalyanaraman, Balaraman, Kaminskyy, Danylo, Karbaschi, Mahsa, Kleanthous, Marina, Klotz, Lars-Oliver, Korac, Bato, Korkmaz, Kemal Sami, Koziel, Rafal, Kračun, Damir, Krause, Karl-Heinz, Křen, Vladimír, Krieg, Thomas, Laranjinha, João, Lazou, Antigone, Li, Huige, Martínez-Ruiz, Antonio, Matsui, Reiko, Mcbean, Gethin J., Meredith, Stuart P., Messens, Joris, Miguel, Verónica, Mikhed, Yuliya, Milisav, Irina, Milković, Lidija, Miranda-Vizuete, Antonio, Mojović, Milos, Monsalve, María, Mouthuy, Pierre-Alexis, Mulvey, John, Münzel, Thomas, Muzykantov, Vladimir, Nguyen, Isabel T.N., Oelze, Matthias, Oliveira, Nuno G., Palmeira, Carlos M., Papaevgeniou, Nikoletta, Pavićević, Aleksandra, Pedre, Brandán, Peyrot, Fabienne, Phylactides, Marios, Pircalabioru, Gratiela G., Pitt, Andrew R., Poulsen, Henrik E., Prieto, Ignacio, Rigobello, Maria Pia, Robledinos-Antón, Natalia, Rodríguez-mañas, Leocadio, Rolo, Anabela P., Rousset, Francis, Ruskovska, Tatjana, Saraiva, Nuno, Sasson, Shlomo, Schröder, Katrin, Semen, Khrystyna, Seredenina, Tamara, Shakirzyanova, Anastasia, Smith, Geoffrey L., Soldati, Thierry, Sousa, Bebiana C., Spickett, Corinne M., Stancic, Ana, Stasia, Marie José, Steinbrenner, Holger, Stepanić, Višnja, Steven, Sebastian, Tokatlidis, Kostas, Tuncay, Erkan, Turan, Belma, Ursini, Fulvio, Vacek, Jan, Vajnerova, Olga, Valentová, Kateřina, van Breusegem, Frank, Varisli, Lokman, Veal, Elizabeth A., Yalçın, A. Suha, Yelisyeyeva, Olha, Žarković, Neven, Zatloukalová, Martina, Zielonka, Jacek, Touyz, Rhian M., Papapetropoulos, Andreas, Grune, Tilman, Lamas, Santiago, Schmidt, Harald H.H.W., di Lisa, Fabio, and Daiber, Andreas

Abstract

The European Cooperation in Science and Technology (COST) provides an ideal framework to establish multi-disciplinary research networks. COST Action BM1203 (EU-ROS) represents a consortium of researchers from different disciplines who are dedicated to providing new insights and tools for better understanding redox biology and medicine and, in the long run, to finding new therapeutic strategies to target dysregulated redox processes in various diseases. This report highlights the major achievements of EU-ROS as well as research updates and new perspectives arising from its members. The EU-ROS consortium comprised more than 140 active members who worked together for four years on the topics briefly described below. The formation of reactive oxygen and nitrogen species (RONS) is an established hallmark of our aerobic environment and metabolism but RONS also act as messengers via redox regulation of essential cellular processes. The fact that many diseases have been found to be associated with oxidative stress established the theory of oxidative stress as a trigger of diseases that can be corrected by antioxidant therapy. However, while experimental studies support this thesis, clinical studies still generate controversial results, due to complex pathophysiology of oxidative stress in humans. For future improvement of antioxidant therapy and better understanding of redox-associated disease progression detailed knowledge on the sources and targets of RONS formation and discrimination of their detrimental or beneficial roles is required. In order to advance this important area of biology and medicine, highly synergistic approaches combining a variety of diverse and contrasting disciplines are needed.

Published
2017

12. European contribution to the study of ROS : A summary of the findings and prospects for the future from the COST action BM1203 (EU-ROS)

Author

Egea, Javier, Fabregat, Isabel, Frapart, Yves M, Ghezzi, Pietro, Görlach, Agnes, Kietzmann, Thomas, Kubaichuk, Kateryna, Knaus, Ulla G, Lopez, Manuela G, Olaso-Gonzalez, Gloria, Petry, Andreas, Schulz, Rainer, Vina, Jose, Winyard, Paul J, Abbas, Kahina, Ademowo, Opeyemi S, Afonso, Catarina B, Andreadou, Ioanna, Antelmann, Haike, Antunes, Fernando, Aslan, Mutay, Bachschmid, Markus M, Barbosa, Rui M, Belousov, Vsevolod, Berndt, Carsten, Bernlohr, David, Bertrán, Esther, Bindoli, Alberto, Bottari, Serge P, Brito, Paula M, Carrara, Guia, Casas, Ana I, Chatzi, Afroditi, Chondrogianni, Niki, Conrad, Marcus, Cooke, Marcus S, Costa, João G, Cuadrado, Antonio, My-Chan Dang, Pham, De Smet, Barbara, Debelec-Butuner, Bilge, Dias, Irundika H K, Dunn, Joe Dan, Edson, Amanda J, El Assar, Mariam, El-Benna, Jamel, Ferdinandy, Péter, Fernandes, Ana S, Fladmark, Kari E, Förstermann, Ulrich, Giniatullin, Rashid, Giricz, Zoltán, Görbe, Anikó, Griffiths, Helen L, Hampl, Vaclav, Hanf, Alina, Herget, Jan, Hernansanz-Agustín, Pablo, Hillion, Melanie, Huang, Jingjing, Ilikay, Serap, Jansen-Dürr, Pidder, Jaquet, Vincent, Joles, Jaap A, Kalyanaraman, Balaraman, Kaminskyy, Danylo, Karbaschi, Mahsa, Kleanthous, Marina, Klotz, Lars-Oliver, Korac, Bato, Korkmaz, Kemal Sami, Koziel, Rafal, Kračun, Damir, Krause, Karl-Heinz, Křen, Vladimír, Krieg, Thomas, Laranjinha, João, Lazou, Antigone, Li, Huige, Martínez-Ruiz, Antonio, Matsui, Reiko, McBean, Gethin J, Meredith, Stuart P, Messens, Joris, Miguel, Verónica, Mikhed, Yuliya, Milisav, Irina, Milković, Lidija, Miranda-Vizuete, Antonio, Mojović, Miloš, Monsalve, María, Mouthuy, Pierre-Alexis, Mulvey, John, Münzel, Thomas, Muzykantov, Vladimir, Nguyen, Isabel T N, Oelze, Matthias, Oliveira, Nuno G, Palmeira, Carlos M, Papaevgeniou, Nikoletta, Pavićević, Aleksandra, Pedre, Brandán, Peyrot, Fabienne, Phylactides, Marios, Pircalabioru, Gratiela G, Pitt, Andrew R, Poulsen, Henrik E, Prieto, Ignacio, Rigobello, Maria Pia, Robledinos-Antón, Natalia, Rodríguez-Mañas, Leocadio, Rolo, Anabela P, Rousset, Francis, Ruskovska, Tatjana, Saraiva, Nuno, Sasson, Shlomo, Schröder, Katrin, Semen, Khrystyna, Seredenina, Tamara, Shakirzyanova, Anastasia, Smith, Geoffrey L, Soldati, Thierry, Sousa, Bebiana C, Spickett, Corinne M, Stancic, Ana, Stasia, Marie José, Steinbrenner, Holger, Stepanić, Višnja, Steven, Sebastian, Tokatlidis, Kostas, Tuncay, Erkan, Turan, Belma, Ursini, Fulvio, Vacek, Jan, Vajnerova, Olga, Valentová, Kateřina, Van Breusegem, Frank, Varisli, Lokman, Veal, Elizabeth A, Yalçın, A Suha, Yelisyeyeva, Olha, Žarković, Neven, Zatloukalová, Martina, Zielonka, Jacek, Touyz, Rhian M, Papapetropoulos, Andreas, Grune, Tilman, Lamas, Santiago, Schmidt, Harald H H W, Di Lisa, Fabio, Daiber, Andreas, Egea, Javier, Fabregat, Isabel, Frapart, Yves M, Ghezzi, Pietro, Görlach, Agnes, Kietzmann, Thomas, Kubaichuk, Kateryna, Knaus, Ulla G, Lopez, Manuela G, Olaso-Gonzalez, Gloria, Petry, Andreas, Schulz, Rainer, Vina, Jose, Winyard, Paul J, Abbas, Kahina, Ademowo, Opeyemi S, Afonso, Catarina B, Andreadou, Ioanna, Antelmann, Haike, Antunes, Fernando, Aslan, Mutay, Bachschmid, Markus M, Barbosa, Rui M, Belousov, Vsevolod, Berndt, Carsten, Bernlohr, David, Bertrán, Esther, Bindoli, Alberto, Bottari, Serge P, Brito, Paula M, Carrara, Guia, Casas, Ana I, Chatzi, Afroditi, Chondrogianni, Niki, Conrad, Marcus, Cooke, Marcus S, Costa, João G, Cuadrado, Antonio, My-Chan Dang, Pham, De Smet, Barbara, Debelec-Butuner, Bilge, Dias, Irundika H K, Dunn, Joe Dan, Edson, Amanda J, El Assar, Mariam, El-Benna, Jamel, Ferdinandy, Péter, Fernandes, Ana S, Fladmark, Kari E, Förstermann, Ulrich, Giniatullin, Rashid, Giricz, Zoltán, Görbe, Anikó, Griffiths, Helen L, Hampl, Vaclav, Hanf, Alina, Herget, Jan, Hernansanz-Agustín, Pablo, Hillion, Melanie, Huang, Jingjing, Ilikay, Serap, Jansen-Dürr, Pidder, Jaquet, Vincent, Joles, Jaap A, Kalyanaraman, Balaraman, Kaminskyy, Danylo, Karbaschi, Mahsa, Kleanthous, Marina, Klotz, Lars-Oliver, Korac, Bato, Korkmaz, Kemal Sami, Koziel, Rafal, Kračun, Damir, Krause, Karl-Heinz, Křen, Vladimír, Krieg, Thomas, Laranjinha, João, Lazou, Antigone, Li, Huige, Martínez-Ruiz, Antonio, Matsui, Reiko, McBean, Gethin J, Meredith, Stuart P, Messens, Joris, Miguel, Verónica, Mikhed, Yuliya, Milisav, Irina, Milković, Lidija, Miranda-Vizuete, Antonio, Mojović, Miloš, Monsalve, María, Mouthuy, Pierre-Alexis, Mulvey, John, Münzel, Thomas, Muzykantov, Vladimir, Nguyen, Isabel T N, Oelze, Matthias, Oliveira, Nuno G, Palmeira, Carlos M, Papaevgeniou, Nikoletta, Pavićević, Aleksandra, Pedre, Brandán, Peyrot, Fabienne, Phylactides, Marios, Pircalabioru, Gratiela G, Pitt, Andrew R, Poulsen, Henrik E, Prieto, Ignacio, Rigobello, Maria Pia, Robledinos-Antón, Natalia, Rodríguez-Mañas, Leocadio, Rolo, Anabela P, Rousset, Francis, Ruskovska, Tatjana, Saraiva, Nuno, Sasson, Shlomo, Schröder, Katrin, Semen, Khrystyna, Seredenina, Tamara, Shakirzyanova, Anastasia, Smith, Geoffrey L, Soldati, Thierry, Sousa, Bebiana C, Spickett, Corinne M, Stancic, Ana, Stasia, Marie José, Steinbrenner, Holger, Stepanić, Višnja, Steven, Sebastian, Tokatlidis, Kostas, Tuncay, Erkan, Turan, Belma, Ursini, Fulvio, Vacek, Jan, Vajnerova, Olga, Valentová, Kateřina, Van Breusegem, Frank, Varisli, Lokman, Veal, Elizabeth A, Yalçın, A Suha, Yelisyeyeva, Olha, Žarković, Neven, Zatloukalová, Martina, Zielonka, Jacek, Touyz, Rhian M, Papapetropoulos, Andreas, Grune, Tilman, Lamas, Santiago, Schmidt, Harald H H W, Di Lisa, Fabio, and Daiber, Andreas

Published
2017

13. European contribution to the study of ROS: A summary of the findings and prospects for the future from the COST action BM1203 (EU-ROS)

Author

MS Nefrologie, Regenerative Medicine and Stem Cells, Circulatory Health, Nefro Vasculaire Geneeskunde, Other research (not in main researchprogram), Egea, Javier, Fabregat, Isabel, Frapart, Yves M, Ghezzi, Pietro, Görlach, Agnes, Kietzmann, Thomas, Kubaichuk, Kateryna, Knaus, Ulla G, Lopez, Manuela G, Olaso-Gonzalez, Gloria, Petry, Andreas, Schulz, Rainer, Vina, Jose, Winyard, Paul J, Abbas, Kahina, Ademowo, Opeyemi S, Afonso, Catarina B, Andreadou, Ioanna, Antelmann, Haike, Antunes, Fernando, Aslan, Mutay, Bachschmid, Markus M, Barbosa, Rui M, Belousov, Vsevolod, Berndt, Carsten, Bernlohr, David, Bertrán, Esther, Bindoli, Alberto, Bottari, Serge P, Brito, Paula M, Carrara, Guia, Casas, Ana I, Chatzi, Afroditi, Chondrogianni, Niki, Conrad, Marcus, Cooke, Marcus S, Costa, João G, Cuadrado, Antonio, My-Chan Dang, Pham, De Smet, Barbara, Debelec-Butuner, Bilge, Dias, Irundika H K, Dunn, Joe Dan, Edson, Amanda J, El Assar, Mariam, El-Benna, Jamel, Ferdinandy, Péter, Fernandes, Ana S, Fladmark, Kari E, Förstermann, Ulrich, Giniatullin, Rashid, Giricz, Zoltán, Görbe, Anikó, Griffiths, Helen L, Hampl, Vaclav, Hanf, Alina, Herget, Jan, Hernansanz-Agustín, Pablo, Hillion, Melanie, Huang, Jingjing, Ilikay, Serap, Jansen-Dürr, Pidder, Jaquet, Vincent, Joles, Jaap A, Kalyanaraman, Balaraman, Kaminskyy, Danylo, Karbaschi, Mahsa, Kleanthous, Marina, Klotz, Lars-Oliver, Korac, Bato, Korkmaz, Kemal Sami, Koziel, Rafal, Kračun, Damir, Krause, Karl-Heinz, Křen, Vladimír, Krieg, Thomas, Laranjinha, João, Lazou, Antigone, Li, Huige, Martínez-Ruiz, Antonio, Matsui, Reiko, McBean, Gethin J, Meredith, Stuart P, Messens, Joris, Miguel, Verónica, Mikhed, Yuliya, Milisav, Irina, Milković, Lidija, Miranda-Vizuete, Antonio, Mojović, Miloš, Monsalve, María, Mouthuy, Pierre-Alexis, Mulvey, John, Münzel, Thomas, Muzykantov, Vladimir, Nguyen, Isabel T N, Oelze, Matthias, Oliveira, Nuno G, Palmeira, Carlos M, Papaevgeniou, Nikoletta, Pavićević, Aleksandra, Pedre, Brandán, Peyrot, Fabienne, Phylactides, Marios, Pircalabioru, Gratiela G, Pitt, Andrew R, Poulsen, Henrik E, Prieto, Ignacio, Rigobello, Maria Pia, Robledinos-Antón, Natalia, Rodríguez-Mañas, Leocadio, Rolo, Anabela P, Rousset, Francis, Ruskovska, Tatjana, Saraiva, Nuno, Sasson, Shlomo, Schröder, Katrin, Semen, Khrystyna, Seredenina, Tamara, Shakirzyanova, Anastasia, Smith, Geoffrey L, Soldati, Thierry, Sousa, Bebiana C, Spickett, Corinne M, Stancic, Ana, Stasia, Marie José, Steinbrenner, Holger, Stepanić, Višnja, Steven, Sebastian, Tokatlidis, Kostas, Tuncay, Erkan, Turan, Belma, Ursini, Fulvio, Vacek, Jan, Vajnerova, Olga, Valentová, Kateřina, Van Breusegem, Frank, Varisli, Lokman, Veal, Elizabeth A, Yalçın, A Suha, Yelisyeyeva, Olha, Žarković, Neven, Zatloukalová, Martina, Zielonka, Jacek, Touyz, Rhian M, Papapetropoulos, Andreas, Grune, Tilman, Lamas, Santiago, Schmidt, Harald H H W, Di Lisa, Fabio, Daiber, Andreas, MS Nefrologie, Regenerative Medicine and Stem Cells, Circulatory Health, Nefro Vasculaire Geneeskunde, Other research (not in main researchprogram), Egea, Javier, Fabregat, Isabel, Frapart, Yves M, Ghezzi, Pietro, Görlach, Agnes, Kietzmann, Thomas, Kubaichuk, Kateryna, Knaus, Ulla G, Lopez, Manuela G, Olaso-Gonzalez, Gloria, Petry, Andreas, Schulz, Rainer, Vina, Jose, Winyard, Paul J, Abbas, Kahina, Ademowo, Opeyemi S, Afonso, Catarina B, Andreadou, Ioanna, Antelmann, Haike, Antunes, Fernando, Aslan, Mutay, Bachschmid, Markus M, Barbosa, Rui M, Belousov, Vsevolod, Berndt, Carsten, Bernlohr, David, Bertrán, Esther, Bindoli, Alberto, Bottari, Serge P, Brito, Paula M, Carrara, Guia, Casas, Ana I, Chatzi, Afroditi, Chondrogianni, Niki, Conrad, Marcus, Cooke, Marcus S, Costa, João G, Cuadrado, Antonio, My-Chan Dang, Pham, De Smet, Barbara, Debelec-Butuner, Bilge, Dias, Irundika H K, Dunn, Joe Dan, Edson, Amanda J, El Assar, Mariam, El-Benna, Jamel, Ferdinandy, Péter, Fernandes, Ana S, Fladmark, Kari E, Förstermann, Ulrich, Giniatullin, Rashid, Giricz, Zoltán, Görbe, Anikó, Griffiths, Helen L, Hampl, Vaclav, Hanf, Alina, Herget, Jan, Hernansanz-Agustín, Pablo, Hillion, Melanie, Huang, Jingjing, Ilikay, Serap, Jansen-Dürr, Pidder, Jaquet, Vincent, Joles, Jaap A, Kalyanaraman, Balaraman, Kaminskyy, Danylo, Karbaschi, Mahsa, Kleanthous, Marina, Klotz, Lars-Oliver, Korac, Bato, Korkmaz, Kemal Sami, Koziel, Rafal, Kračun, Damir, Krause, Karl-Heinz, Křen, Vladimír, Krieg, Thomas, Laranjinha, João, Lazou, Antigone, Li, Huige, Martínez-Ruiz, Antonio, Matsui, Reiko, McBean, Gethin J, Meredith, Stuart P, Messens, Joris, Miguel, Verónica, Mikhed, Yuliya, Milisav, Irina, Milković, Lidija, Miranda-Vizuete, Antonio, Mojović, Miloš, Monsalve, María, Mouthuy, Pierre-Alexis, Mulvey, John, Münzel, Thomas, Muzykantov, Vladimir, Nguyen, Isabel T N, Oelze, Matthias, Oliveira, Nuno G, Palmeira, Carlos M, Papaevgeniou, Nikoletta, Pavićević, Aleksandra, Pedre, Brandán, Peyrot, Fabienne, Phylactides, Marios, Pircalabioru, Gratiela G, Pitt, Andrew R, Poulsen, Henrik E, Prieto, Ignacio, Rigobello, Maria Pia, Robledinos-Antón, Natalia, Rodríguez-Mañas, Leocadio, Rolo, Anabela P, Rousset, Francis, Ruskovska, Tatjana, Saraiva, Nuno, Sasson, Shlomo, Schröder, Katrin, Semen, Khrystyna, Seredenina, Tamara, Shakirzyanova, Anastasia, Smith, Geoffrey L, Soldati, Thierry, Sousa, Bebiana C, Spickett, Corinne M, Stancic, Ana, Stasia, Marie José, Steinbrenner, Holger, Stepanić, Višnja, Steven, Sebastian, Tokatlidis, Kostas, Tuncay, Erkan, Turan, Belma, Ursini, Fulvio, Vacek, Jan, Vajnerova, Olga, Valentová, Kateřina, Van Breusegem, Frank, Varisli, Lokman, Veal, Elizabeth A, Yalçın, A Suha, Yelisyeyeva, Olha, Žarković, Neven, Zatloukalová, Martina, Zielonka, Jacek, Touyz, Rhian M, Papapetropoulos, Andreas, Grune, Tilman, Lamas, Santiago, Schmidt, Harald H H W, Di Lisa, Fabio, and Daiber, Andreas

Published
2017

14. Sulfur-containing amino acids: a neurochemical perspective

Author

McBean, Gethin J.

Subjects
Cysteine uptake, Brain diseases
Abstract

This review charts recent developments in understanding the neurochemistry of endogenous sulfur-containing amino acids as neuromodulators, metabolic intermediates and potential toxins. The amino acids discussed include L-cysteine, L-cysteine sulfinic acid, L-cysteic acid, L-homocysteine, L-homocysteine sulfinic acid, L-homocysteic acid and taurine. Particular emphasis is placed on examining the mechanism and regulation of biochemical pathways that contribute to the synthesis and metabolism of cysteine, especially in its capacity as precursor of glutathione, taurine and hydrogen sulfide. Evidence concerning the role of cysteine and its oxidised form, cystine, in the control of intracellular and extracellular redox potentials and in the response of cells to oxidative stress is presented. Lastly, the therapeutic potential of intervention in the pathways of sulfur-containing amino acid metabolism in the brain is discussed.

Published
2016

15. European contribution to the study of ROS: A summary of the findings and prospects for the future from the COST action BM1203 (EU-ROS)

Author

Egea, Javier, primary, Fabregat, Isabel, additional, Frapart, Yves M., additional, Ghezzi, Pietro, additional, Görlach, Agnes, additional, Kietzmann, Thomas, additional, Kubaichuk, Kateryna, additional, Knaus, Ulla G., additional, Lopez, Manuela G., additional, Olaso-Gonzalez, Gloria, additional, Petry, Andreas, additional, Schulz, Rainer, additional, Vina, Jose, additional, Winyard, Paul, additional, Abbas, Kahina, additional, Ademowo, Opeyemi S., additional, Afonso, Catarina B., additional, Andreadou, Ioanna, additional, Antelmann, Haike, additional, Antunes, Fernando, additional, Aslan, Mutay, additional, Bachschmid, Markus M., additional, Barbosa, Rui M., additional, Belousov, Vsevolod, additional, Berndt, Carsten, additional, Bernlohr, David, additional, Bertrán, Esther, additional, Bindoli, Alberto, additional, Bottari, Serge P., additional, Brito, Paula M., additional, Carrara, Guia, additional, Casas, Ana I., additional, Chatzi, Afroditi, additional, Chondrogianni, Niki, additional, Conrad, Marcus, additional, Cooke, Marcus S., additional, Costa, João G., additional, Cuadrado, Antonio, additional, My-Chan Dang, Pham, additional, De Smet, Barbara, additional, Debelec–Butuner, Bilge, additional, Dias, Irundika H.K., additional, Dunn, Joe Dan, additional, Edson, Amanda J., additional, El Assar, Mariam, additional, El-Benna, Jamel, additional, Ferdinandy, Péter, additional, Fernandes, Ana S., additional, Fladmark, Kari E., additional, Förstermann, Ulrich, additional, Giniatullin, Rashid, additional, Giricz, Zoltán, additional, Görbe, Anikó, additional, Griffiths, Helen, additional, Hampl, Vaclav, additional, Hanf, Alina, additional, Herget, Jan, additional, Hernansanz-Agustín, Pablo, additional, Hillion, Melanie, additional, Huang, Jingjing, additional, Ilikay, Serap, additional, Jansen-Dürr, Pidder, additional, Jaquet, Vincent, additional, Joles, Jaap A., additional, Kalyanaraman, Balaraman, additional, Kaminskyy, Danylo, additional, Karbaschi, Mahsa, additional, Kleanthous, Marina, additional, Klotz, Lars-Oliver, additional, Korac, Bato, additional, Korkmaz, Kemal Sami, additional, Koziel, Rafal, additional, Kračun, Damir, additional, Krause, Karl-Heinz, additional, Křen, Vladimír, additional, Krieg, Thomas, additional, Laranjinha, João, additional, Lazou, Antigone, additional, Li, Huige, additional, Martínez-Ruiz, Antonio, additional, Matsui, Reiko, additional, McBean, Gethin J., additional, Meredith, Stuart P., additional, Messens, Joris, additional, Miguel, Verónica, additional, Mikhed, Yuliya, additional, Milisav, Irina, additional, Milković, Lidija, additional, Miranda-Vizuete, Antonio, additional, Mojović, Miloš, additional, Monsalve, María, additional, Mouthuy, Pierre-Alexis, additional, Mulvey, John, additional, Münzel, Thomas, additional, Muzykantov, Vladimir, additional, Nguyen, Isabel T.N., additional, Oelze, Matthias, additional, Oliveira, Nuno G., additional, Palmeira, Carlos M., additional, Papaevgeniou, Nikoletta, additional, Pavićević, Aleksandra, additional, Pedre, Brandán, additional, Peyrot, Fabienne, additional, Phylactides, Marios, additional, Pircalabioru, Gratiela G., additional, Pitt, Andrew R., additional, Poulsen, Henrik E., additional, Prieto, Ignacio, additional, Rigobello, Maria Pia, additional, Robledinos-Antón, Natalia, additional, Rodríguez-Mañas, Leocadio, additional, Rolo, Anabela P., additional, Rousset, Francis, additional, Ruskovska, Tatjana, additional, Saraiva, Nuno, additional, Sasson, Shlomo, additional, Schröder, Katrin, additional, Semen, Khrystyna, additional, Seredenina, Tamara, additional, Shakirzyanova, Anastasia, additional, Smith, Geoffrey L., additional, Soldati, Thierry, additional, Sousa, Bebiana C., additional, Spickett, Corinne M., additional, Stancic, Ana, additional, Stasia, Marie José, additional, Steinbrenner, Holger, additional, Stepanić, Višnja, additional, Steven, Sebastian, additional, Tokatlidis, Kostas, additional, Tuncay, Erkan, additional, Turan, Belma, additional, Ursini, Fulvio, additional, Vacek, Jan, additional, Vajnerova, Olga, additional, Valentová, Kateřina, additional, Van Breusegem, Frank, additional, Varisli, Lokman, additional, Veal, Elizabeth A., additional, Yalçın, A. Suha, additional, Yelisyeyeva, Olha, additional, Žarković, Neven, additional, Zatloukalová, Martina, additional, Zielonka, Jacek, additional, Touyz, Rhian M., additional, Papapetropoulos, Andreas, additional, Grune, Tilman, additional, Lamas, Santiago, additional, Schmidt, Harald H.H.W., additional, Di Lisa, Fabio, additional, and Daiber, Andreas, additional

Published
2017
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16. Thiol redox homeostasis in neurodegenerative disease

Author

McBean, Gethin J., Aslan, Mutay, Griffiths, Helen R., Torrão, Rita C, McBean, Gethin J., Aslan, Mutay, Griffiths, Helen R., and Torrão, Rita C

Abstract

This review provides an overview of the biochemistry of thiol redox couples and the significance of thiol redox homeostasis in neurodegenerative disease. The discussion is centred on cysteine/cystine redox balance, the significance of the xc- cystine-glutamate exchanger and the association between protein thiol redox balance and neurodegeneration, with particular reference to Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and glaucoma. The role of thiol disulphide oxidoreductases in providing neuroprotection is also discussed.

Published
2015

17. The thiol redox system in glioma biology : clinical target and significance in resistance to glioma chemotherapy

Author

McBean, Gethin J.

Subjects
Transsulfuration, Oxidoreductase, xCT, GSH, Cystine-glutamate exchanger, Glioma, Cysteine, Astrocyte
Abstract

Sulfur-containing compounds play an essential role in maintaining redox balance in glioma cells. Chief amongst these are the reduced and oxidised (disulfide) forms of cysteine (cysteine/cystine) and glutathione (GSH /GSSG) as well as thioredoxin and glutaredoxin, members of the thiol-disulfide oxidoreductases. GSH is also important as an antioxidant, as a ‘safe’ storage form of cysteine and for detoxification reactions involving the GSH sulfur transferase family of enzymes. Glioma cells contain a high concentration of GSH, compared to normal astrocytes, which renders these cells particularly resistant to chemotherapeutic agents. The rate of synthesis of GSH is controlled by the availability of cysteine, which is imported in its oxidised form, cystine, through specialized channels in the plasma membrane. These channels, known as the cystine-glutamate xc- exchanger, operate by taking up cystine in exchange for glutamate, which is released into the extracellular medium. Glioma cells export large quantities of glutamate by this mechanism, which, if unchecked, causes damage and eventual death of surrounding neurones. Thus, GSH synthesis in glioma cells fuels resistance to chemotherapy and, at the same time, kills off surrounding neurones thereby providing space for tumor cell growth. Much is now known of the molecular mechanism of cystine import and of GSH synthesis in glioma cells. In particular, a number of therapeutic strategies that target the cystine-glutamate exchanger have been proposed on the basis that this would inhibit synthesis of GSH and remove the source of glutamate release. This review describes new developments in the field of glioma cell redox balance and evaluates the potential for clinical intervention at the level of cysteine and GSH biosynthesis that may prove effective in combating brain tumor growth and development. TS 31.07.13

Published
2013

18. Astrocytes and the regulation of cerebral cysteine/cystine redox potential: implications for cysteine neurotoxicity

Author

McBean, Gethin J.

Subjects
Redox, Neurotoxicology, Oxidation-reduction reaction, Oxidative stress, Nervous system--Degeneration, Neurotoxicity, Cystine, Cysteine, Neurodegeneration, Glutathione, Cysteine proteinases
Abstract

The sulfur amino acid, cysteine plays an essential role in maintaining cellular redox potential and is a key constituent of the antioxidant, glutathione. Cysteine is highly reactive and readily oxidises to the disulfide form, cystine, producing oxygen radicals as a by-product. Extracellular oxidising conditions favour cystine, whereas cysteine is the dominant intracellular form of the amino acid. In the brain, astrocytes control the extracellular thiol redox potential by actively taking up cystine and exporting cysteine. Particularly, astrocytes up-regulate the cysteine/cystine cycle in response to oxidative stress, which is essential for preventing damage to neuronal function arising from loss of redox balance. Recent evidence shows that the extracellular cysteine/cystine redox state may have a significant role in a number of processes that affect synaptic activity, including signal transduction and receptor activation and may be implicated in a number of neurodegenerative diseases, for example Alzheimer’s and Parkinson’s. This review charts recent developments in understanding the role of astrocytes in neuroprotection via management of the extracellular thiol redox potential in normal brain function and provides an up-to-date account of cysteine neurotoxicity and its significance in the aetiology of neurodegenerative disease. Science Foundation Ireland

Published
2012

20. Cysteine, Glutathione, and Thiol Redox Balance in Astrocytes.

Author

McBean, Gethin J.

Subjects
ASTROCYTES, CYSTEINE, GLUTATHIONE, THIOLS, OXIDATION-reduction reaction
Abstract

This review discusses the current understanding of cysteine and glutathione redox balance in astrocytes. Particular emphasis is placed on the impact of oxidative stress and astrocyte activation on pathways that provide cysteine as a precursor for glutathione. The effect of the disruption of thiol-containing amino acid metabolism on the antioxidant capacity of astrocytes is also discussed. [ABSTRACT FROM AUTHOR]

Published
2017
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35. An investigation into the role of calcium in the modulation of rat synaptosomal d-[3H]aspartate transport by docosahexaenoic acid

Author

Berry, Colm B. and McBean, Gethin J.

Subjects
*UNSATURATED fatty acids, *SYNAPTOSOMES
Abstract

The effect of the polyunsaturated fatty acid cis-4,7,10,13,16,19-docosahexaenoic acid (DHA) on the high-affinity, sodium-dependent uptake of d-[3H]aspartate into purified rat brain synaptosomes was examined. Incubation of the synaptosomes with 20 μM DHA caused over 50% inhibition of the maximum velocity (Vmax) of d-[3H]aspartate transport. This inhibition was significantly potentiated by pre-exposure of the synaptosomes to the fatty acid for 10 min prior to the start of the transport assay. Less highly unsaturated fatty acids such as arachidonic acid (cis-5,8,11,14-eicosatetraenoic acid), linolenic acid (cis-9,12,15-octadecatrienoic acid) and oleic acid (cis-9-octadecenoic acid) were significantly less potent than DHA. Removal of extracellular calcium, or reduction of the intracellular calcium concentration using the intracellular calcium chelator BAPTA/AM (10 μM), did not reduce the inhibition caused by DHA. On the other hand, an increase in the concentration of intracellular calcium mediated by thapsigargin (25 μM) or the calcium ionophore A23187 (10 or 100 nM) led to a reduction in the rate of d-[3H]aspartate transport in the absence of DHA. The CaM kinase II inhibitor, KN-93, reduced d-[3H]aspartate uptake independently of whether DHA was also present, but had no effect on the inhibition of d-[3H]aspartate uptake by either A23187 or thapsigargin. We conclude that whereas DHA inhibits synaptosomal d-[3H]aspartate uptake in a calcium-independent manner, a calcium-based mechanism exists that can also modulate glutamate transporter activity. [Copyright &y& Elsevier]

Published
2003
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37. In vitroneuronal and vascular responses to 5‐HT in rats chronically exposed to MDMA

Author

Cannon, Dara M, Keenan, Alan K, Guiry, Patrick J, Buon, Christophe, Baird, Alan W, and McBean, Gethin J

Abstract

This study examined the effects of chronic exposure of rats to 3,4‐methylenedioxymethamphetamine (MDMA) on [3H]5‐hydroxytryptamine ([3H]5‐HT) re‐uptake into purified rat brain synaptosomes, 5‐HT‐induced isometric contraction of aortic rings and [3H]5‐HT re‐uptake into rat aorta.Rats were administered MDMA (20 mg kg−1i.p.) twice daily over 4 days. One, 7, 14 or 21 days post treatment, whole brain synaptosomes and descending thoracic aortic rings were prepared for investigation.Chronic MDMA treatment significantly reduced the maximum rate (Vmax) of specific high‐affinity [3H]5‐HT re‐uptake 1 day after treatment and for up to 21 days post‐final administration of MDMA. Direct application of MDMA (100 μM) abolished synaptosomal re‐uptake of [3H]5‐HT in vitro.Chronic MDMA administration significantly reduced the maximum contraction (Emax) to 5‐HT at 1 and 7 days after treatment, but not at 14 or 21 days.Chronic MDMA administration had no effect on sodium‐dependent [3H]5‐HT re‐uptake into aorta 1 day after treatment, nor did 100 μMMDMA have any direct effect on [3H]5‐HT uptake into aortic rings in vitro.These results show, for the first time, an altered responsiveness of vascular tissue to MDMA after chronic administration. In addition, they demonstrate a difference in the sensitivity of central and peripheral 5‐HT uptake systems to chronic MDMA exposure, and suggest that the action of MDMA in the cardiovascular system does not arise from a direct effect of MDMA on peripheral 5‐HT transport.

Published
2001
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38. Pre-incubation of synaptosomes with arachidonic acid potentiates inhibition of [ 3 H] D -aspartate transport

Author

Lundy, Denise F. and McBean, Gethin J.

Abstract

The ability of low micromolar concentrations of the polyunsaturated fatty acid, arachidonic acid (cis-5,8,11,14-eicosatetraenoic acid) to inhibit the high-affinity, sodium-dependent transport of [ 3 H] D -aspartate into purified synaptosomes of rat brain has been examined. Pre-incubation of the synaptosomes with arachidonic acid for 10-60 min produced a marked potentiation of the response to 10 μM arachidonic acid compared to co-incubation, and the threshold for inhibition of [ 3 H] D -aspartate transport occurred at a concentration of 1 μM. Minimal inhibition of transport was seen with the unsaturated fatty acids, cis-oleic (cis-9-octadecenoic acid) and cis-linolenic (cis-9,12,15-octadecatrienoic acid),nor with the 20-carbon saturated fatty acid, arachidic acid (n- eicosanoic acid ) . Inclusion of the cyclo-oxygenase inhibitor, nor-dihydroguaretic acid (NDGA), in the presence of 5 μM arachidonic acid did not alter the inhibition of [ 3 H] D -aspartate transport between 0-10 min, but did enhance the response at longer pre-incubation times. Inhibition of [ 3 H] D -aspartate transport by arachidonic acid persisted during addition of the calcium ionophore, A23187, whereas removal of calcium ions from the incubation medium potentiated the response to arachidonic acid. The results are discussed in terms of the physiological relevance of the inhibition of glutamate transport by arachidonic acid, and suggest that regulation of inhibition of the glutamate transporter by arachidonic acid may be achieved by changes in the extracellular, as well as the intracellular, concentration of calcium ions.

Published
1995
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47. Glutathione depletion causes a JNK and p38MAPK-mediated increase in expression of cystathionine-γ-lyase and upregulation of the transsulfuration pathway in C6 glioma cells

Author

Kandil, Sarah, Brennan, Lorraine, and McBean, Gethin J.

Subjects
*GLUTATHIONE, *CYSTATHIONINE gamma-lyase, *GENETIC regulation, *SULFURATION, *JNK mitogen-activated protein kinases, *GLIOMAS, *ANTIOXIDANTS, *CELL growth, *ASTROCYTOMAS
Abstract

Abstract: Cancer cells have a high demand for cysteine as precursor of the antioxidant, glutathione, that is required to promote cell growth and division. Uptake of cystine by the cystine-glutamate exchanger provides the majority of cysteine, but a significant percentage may be derived from methionine, via a transsulfuration pathway. Our aim was to evaluate the relative contribution of the exchanger and the transsulfuration pathway to glutathione synthesis in astrocytoma/glioblastoma cells, using the C6 glioma cell line as a model system. Blockade of the exchanger with the gliotoxins l-αaminoadipate or l-β-N-oxalylamino-l-alanine (400μM) caused a loss of cellular cysteine and depletion in glutathione to 51% and 54% of control, respectively, after 24h. Inhibition of the transsulfuration pathway with propargylglycine (1mM, 24h) depleted glutathione to 77% of control. Co-incubation of cells with gliotoxin and propargylglycine reduced glutathione to 39% of control at 24h and to 20% at 48h. Expression of cystathionine-γ-lyase, the rate-limiting enzyme of the transsulfuration pathway, was significantly increased following incubation of the cells with gliotoxins. Incubation of C6 cells with diethylmaleate for 3h led to a significant reduction in glutathione (63%), whereas expression of cystathionine-γ-lyase was increased by 1.5-fold. Re-feeding methionine to diethylmaleate-treated cells incubated in the absence of cystine or methionine resulted in a significant recovery in glutathione that was blocked by propargylglycine. Co-incubation of C6 cells with diethylmaleate and the JNK-inhibitor, SP600125, abolished the increase in expression of cystathionine-γ-lyase that had been observed in the presence of diethylmaleate alone. Similar results were obtained with the p38MAPK inhibitor, SB203580. It is concluded that glutathione depletion causes a JNK- and p38MAPK-mediated increase in expression of cystathionine-γ-lyase that promotes flux through the transsulfuration pathway to compensate for loss of glutathione in C6 glioma cells. [Copyright &y& Elsevier]

Published
2010
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48. Transport of l-[14C]cystine and l-[14C]cysteine by subtypes of high affinity glutamate transporters over-expressed in HEK cells

Author

Hayes, Derek, Wießner, Michael, Rauen, Thomas, and McBean, Gethin J.

Subjects
*HOMOCYSTEINE, *GLUTATHIONE, *CELL membranes, *AMINO acids
Abstract

Abstract: Transport of l-cystine across the cell membrane is essential for synthesis of the major cellular antioxidant, glutathione (γ-glutamylcysteinylglycine). In this study, uptake of l-[14C]cystine by three of the high affinity sodium-dependent mammalian glutamate transporters (GLT1, GLAST and EAAC1) individually expressed in HEK cells has been determined. All three transporters display saturable uptake of l-[14C]cystine with Michaelis affinity (K m) constants in the range of 20–110μM. l-Glutamate and l-homocysteate are potent inhibitors of sodium-dependent l-[14C]cystine uptake in HEKGLAST, HEKGLT1 and HEKEAAC1 cells. Reduction of l-[14C]cystine to l-[14C]cysteine in the presence of 1mM cysteinylglycine increases the uptake rate in HEKGLT1, HEKGLAST and HEKEAAC1 cells, but only a small proportion (<10%) of l-[14C]cysteine uptake in HEKGLT1 and HEKGLAST cells occurs by the high affinity glutamate transporters. The majority (>90%) of l-[14C]cysteine transport in these cells is mediated by the ASC transport system. In HEKEAAC1 cells, on the other hand, l-[14C]cysteine is transported equally by the ASC and EAAC1 transporters. l-Homocysteine inhibits l-[14C]cysteine transport in both HEKGLAST and HEKGLT1 cells, but not in HEKEAAC1 cells. It is concluded that the quantity of l-[14C]cyst(e)ine taken up by individual high affinity sodium-dependent glutamate transporters is determined both by the extracellular concentration of amino acids, such as glutamate and homocysteine, and by the extracellular redox potential, which will control the oxidation state of l-cystine. [Copyright &y& Elsevier]

Published
2005
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49. Gliotoxins disrupt alanine metabolism and glutathione production in C6 glioma cells: a 13C NMR spectroscopic study

Author

Brennan, Lorraine, Hewage, Chandralal, Malthouse, J. Paul G., and McBean, Gethin J.

Subjects
*BIOCHEMISTRY, *GLUTATHIONE, *METABOLISM, *ORGANIC acids
Abstract

Gliotoxins are a group of amino acids that are toxic to astrocytes, and are substrates of high-affinity sodium-dependent glutamate transporters. In the present study, C6 glioma cells were preincubated for 20h in the presence of 400μM l-α-aminoadipate, l-serine-O-sulphate, d-aspartate or l-cysteate, as well as in the presence of the poorly transported l-glutamate uptake inhibitor, l-anti-endo-methanopyrrolidine dicarboxylate. In experiments following [3-13C]alanine metabolism, all toxins caused a decreased incorporation of label into glutamate. Production of labelled lactate changed only when cells were incubated in the presence of l-α-aminoadipate or l-serine-O-sulphate. Incubation with l-anti-endo-methanopyrrolidine dicarboxylate caused no change in the amount of label incorporated into either glutamate or lactate. When glutathione production was followed using 1mM [2-13C]glycine, differential effects of the gliotoxins were revealed. Most notably, both l-serine-O-sulphate and l-α-aminoadipate caused significant increases in labelling of glutathione. Once again, l-anti-endo-methanopyrrolidine dicarboxylate was without effect. Overall, we have shown that the gliotoxins cause disruption to alanine metabolism and glutathione production in C6 glioma cells, but that there are notable differences in their mechanisms of action. In the absence of any disruption to metabolism by l-anti-endo-methanopyrrolidine dicarboxylate, it is concluded that their mode of action involves more than inhibition of glutamate transport. [Copyright &y& Elsevier]

Published
2004
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50. An NMR study of alterations in [1-<F>13C</F>]glucose metabolism in C6 glioma cells by gliotoxic amino acids

Author

Brennan, Lorraine, Hewage, Chandralal, Malthouse, J. Paul G., and McBean, Gethin J.

Subjects
*ASTROCYTES, *METABOLISM, *GLIOMAS
Abstract

A series of glutamate analogues, known as gliotoxins, are toxic to astrocytes in culture, and are inhibitors or substrates of high affinity sodium-dependent glutamate transporters. The mechanisms by which these gliotoxins cause toxicity are not fully understood. The effects of a series of gliotoxic amino acids (l-α-aminoadipate, l-serine-O-sulphate, d-aspartate and l-cysteate) on metabolism of [1-13C]glucose were examined in C6 glioma cells using 13C nuclear magnetic resonance (NMR) spectroscopy. The cells were preincubated in the presence of sub toxic concentrations of each gliotoxin (400 μmol/l) for 20 h. This was followed by incubation (4 h) with [1-13C]glucose (5.5 mmol/l) in the presence and absence of each gliotoxin. The incorporation of 13C label into the observed metabolites was analysed. Following preincubation with l-α-aminoadipate, d-aspartate, and l-serine-O-sulphate there was a significant decrease in the incorporation of 13C label into glutamate, alanine and lactate from [1-13C]glucose. In the presence of l-cysteate production of labelled glutamate was decreased, while there was no significant effect on the concentrations of labelled lactate and alanine. There was no change in the quantity of LDH released into the medium after incubation of the cells with any of the gliotoxins. Overall these results indicate that the presence of gliotoxins profoundly alters the flux of glucose to lactate, alanine, aspartate and glutamate. [Copyright &y& Elsevier]

Published
2003
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