Search

Your search keyword '"Nikitopoulou, Efterpi"' showing total 26 results
Start Over Author "Nikitopoulou, Efterpi"
26 results on '"Nikitopoulou, Efterpi"'

1. Mitochondrial dysfunction abrogates dietary lipid processing in enterocytes

Author

Moschandrea, Chrysanthi, Kondylis, Vangelis, Evangelakos, Ioannis, Herholz, Marija, Schneider, Farina, Schmidt, Christina, Yang, Ming, Ehret, Sandra, Heine, Markus, Jaeckstein, Michelle Y., Szczepanowska, Karolina, Schwarzer, Robin, Baumann, Linda, Bock, Theresa, Nikitopoulou, Efterpi, Brodesser, Susanne, Krüger, Marcus, Frezza, Christian, Heeren, Joerg, Trifunovic, Aleksandra, and Pasparakis, Manolis

Published
2024
Full Text
View/download PDF

2. Fumarate induces vesicular release of mtDNA to drive innate immunity

Author

Zecchini, Vincent, Paupe, Vincent, Herranz-Montoya, Irene, Janssen, Joëlle, Wortel, Inge M. N., Morris, Jordan L., Ferguson, Ashley, Chowdury, Suvagata Roy, Segarra-Mondejar, Marc, Costa, Ana S. H., Pereira, Gonçalo C., Tronci, Laura, Young, Timothy, Nikitopoulou, Efterpi, Yang, Ming, Bihary, Dóra, Caicci, Federico, Nagashima, Shun, Speed, Alyson, Bokea, Kalliopi, Baig, Zara, Samarajiwa, Shamith, Tran, Maxine, Mitchell, Thomas, Johnson, Mark, Prudent, Julien, and Frezza, Christian

Published
2023
Full Text
View/download PDF

3. Macrophage fumarate hydratase restrains mtRNA-mediated interferon production

Author

Hooftman, Alexander, Peace, Christian G., Ryan, Dylan G., Day, Emily A., Yang, Ming, McGettrick, Anne F., Yin, Maureen, Montano, Erica N., Huo, Lihong, Toller-Kawahisa, Juliana E., Zecchini, Vincent, Ryan, Tristram A. J., Bolado-Carrancio, Alfonso, Casey, Alva M., Prag, Hiran A., Costa, Ana S. H., De Los Santos, Gabriela, Ishimori, Mariko, Wallace, Daniel J., Venuturupalli, Swamy, Nikitopoulou, Efterpi, Frizzell, Norma, Johansson, Cecilia, Von Kriegsheim, Alexander, Murphy, Michael P., Jefferies, Caroline, Frezza, Christian, and O’Neill, Luke A. J.

Published
2023
Full Text
View/download PDF

4. Dynamic partitioning of branched-chain amino acids-derived nitrogen supports renal cancer progression

Author

Sciacovelli, Marco, Dugourd, Aurelien, Jimenez, Lorea Valcarcel, Yang, Ming, Nikitopoulou, Efterpi, Costa, Ana S. H., Tronci, Laura, Caraffini, Veronica, Rodrigues, Paulo, Schmidt, Christina, Ryan, Dylan Gerard, Young, Timothy, Zecchini, Vincent R., Rossi, Sabrina H., Massie, Charlie, Lohoff, Caroline, Masid, Maria, Hatzimanikatis, Vassily, Kuppe, Christoph, Von Kriegsheim, Alex, Kramann, Rafael, Gnanapragasam, Vincent, Warren, Anne Y., Stewart, Grant D., Erez, Ayelet, Vanharanta, Sakari, Saez-Rodriguez, Julio, and Frezza, Christian

Published
2022
Full Text
View/download PDF

5. Convergent somatic mutations in metabolism genes in chronic liver disease

Author

Ng, Stanley W. K., Rouhani, Foad J., Brunner, Simon F., Brzozowska, Natalia, Aitken, Sarah J., Yang, Ming, Abascal, Federico, Moore, Luiza, Nikitopoulou, Efterpi, Chappell, Lia, Leongamornlert, Daniel, Ivovic, Aleksandra, Robinson, Philip, Butler, Timothy, Sanders, Mathijs A., Williams, Nicholas, Coorens, Tim H. H., Teague, Jon, Raine, Keiran, Butler, Adam P., Hooks, Yvette, Wilson, Beverley, Birtchnell, Natalie, Naylor, Huw, Davies, Susan E., Stratton, Michael R., Martincorena, Iñigo, Rahbari, Raheleh, Frezza, Christian, Hoare, Matthew, and Campbell, Peter J.

Published
2021
Full Text
View/download PDF

6. Bone Marrow Mesenchymal Stem Cells Support Acute Myeloid Leukemia Bioenergetics and Enhance Antioxidant Defense and Escape from Chemotherapy

Author

Forte, Dorian, García-Fernández, María, Sánchez-Aguilera, Abel, Stavropoulou, Vaia, Fielding, Claire, Martín-Pérez, Daniel, López, Juan Antonio, Costa, Ana S.H., Tronci, Laura, Nikitopoulou, Efterpi, Barber, Michael, Gallipoli, Paolo, Marando, Ludovica, Fernández de Castillejo, Carlos López, Tzankov, Alexandar, Dietmann, Sabine, Cavo, Michele, Catani, Lucia, Curti, Antonio, Vázquez, Jesús, Frezza, Christian, Huntly, Brian J., Schwaller, Juerg, and Méndez-Ferrer, Simón

Published
2020
Full Text
View/download PDF

8. Succinate accumulation drives ischaemia-reperfusion injury during organ transplantation

Author

Martin, Jack L., Costa, Ana S. H., Gruszczyk, Anja V., Beach, Timothy E., Allen, Fay M., Prag, Hiran A., Hinchy, Elizabeth C., Mahbubani, Krishnaa, Hamed, Mazin, Tronci, Laura, Nikitopoulou, Efterpi, James, Andrew M., Krieg, Thomas, Robinson, Alan J., Huang, Margaret M., Caldwell, Stuart T., Logan, Angela, Pala, Laura, Hartley, Richard C., Frezza, Christian, Saeb-Parsy, Kourosh, and Murphy, Michael P.

Published
2019
Full Text
View/download PDF

10. Disruption of the TCA cycle reveals an ATF4-dependent integration of redox and amino acid metabolism

Author

Ryan, Dylan Gerard, primary, Yang, Ming, additional, Prag, Hiran A, additional, Blanco, Giovanny Rodriguez, additional, Nikitopoulou, Efterpi, additional, Segarra-Mondejar, Marc, additional, Powell, Christopher A, additional, Young, Tim, additional, Burger, Nils, additional, Miljkovic, Jan Lj, additional, Minczuk, Michal, additional, Murphy, Michael P, additional, von Kriegsheim, Alex, additional, and Frezza, Christian, additional

Published
2021
Full Text
View/download PDF

11. Rapid fractionation of mitochondria from mouse liver and heart reveals in vivo metabolite compartmentation.

Author

Allen, Fay M., Costa, Ana S. H., Gruszczyk, Anja V., Bates, Georgina R., Prag, Hiran A., Nikitopoulou, Efterpi, Viscomi, Carlo, Frezza, Christian, James, Andrew M., and Murphy, Michael P.

Subjects
CELL communication, LIVER, MICE, CYTOSOL, HEAT stroke, HEART, MITOCHONDRIA
Abstract

The compartmentation and distribution of metabolites between mitochondria and the rest of the cell is a key parameter of cell signalling and pathology. Here, we have developed a rapid fractionation procedure that enables us to take mouse heart and liver from in vivo and within ~ 30 s stabilise the distribution of metabolites between mitochondria and the cytosol by rapid cooling, homogenisation and dilution. This is followed by centrifugation of mitochondria through an oil layer to separate mitochondrial and cytosolic fractions for subsequent metabolic analysis. Using this procedure revealed the in vivo compartmentation of mitochondrial metabolites and will enable the assessment of the distribution of metabolites between the cytosol and mitochondria during a range of situations in vivo. [ABSTRACT FROM AUTHOR]

Published
2023
Full Text
View/download PDF

12. Author response: Disruption of the TCA cycle reveals an ATF4-dependent integration of redox and amino acid metabolism

Author

Ryan, Dylan Gerard, primary, Yang, Ming, additional, Prag, Hiran A, additional, Blanco, Giovanny Rodriguez, additional, Nikitopoulou, Efterpi, additional, Segarra-Mondejar, Marc, additional, Powell, Christopher A, additional, Young, Tim, additional, Burger, Nils, additional, Miljkovic, Jan Lj, additional, Minczuk, Michal, additional, Murphy, Michael P, additional, von Kriegsheim, Alex, additional, and Frezza, Christian, additional

Published
2021
Full Text
View/download PDF

13. Lung tumor growth promotion by tobacco-specific nitrosamines involves the β2-adrenergic receptors-dependent stimulation of mitochondrial REDOX signaling

Author

SARLAK, Saharnaz, primary, Lalou, Claude, additional, Bastos Sant'Anna-Silva, Ana Carolina, additional, MAHFOUF, Walid, additional, De Luise, Monica, additional, ROUSSEAU, Benoît, additional, IZOTTE, Julien, additional, CLAVEROL, Stephane, additional, Lacombe, Didier, additional, Nikitopoulou, Efterpi, additional, Yang, Ming, additional, Oliveira, Marcus, additional, Frezza, Christian, additional, Gasparre, Guiseppe, additional, REZVANI, Hamid Reza, additional, AMOEDO, Nivea Dias, additional, and ROSSIGNOL, Rodrigue, additional

Published
2021
Full Text
View/download PDF

14. Nitrogen partitioning between branched-chain amino acids and urea cycle enzymes sustains renal cancer progression

Author

Sciacovelli, Marco, primary, Dugourd, Aurelien, additional, Jimenez, Lorea Valcarcel, additional, Yang, Ming, additional, Nikitopoulou, Efterpi, additional, Costa, Ana S.H., additional, Tronci, Laura, additional, Caraffini, Veronica, additional, Rodrigues, Paulo, additional, Schmidt, Christina, additional, Ryan, Dylan, additional, Young, Tim, additional, Zecchini, Vincent R., additional, Rossi, Sabrina Helena, additional, Massie, Charlie, additional, Lohoff, Caroline, additional, Barcon, Maria Masid, additional, Hatzimanikatis, Vassily, additional, Kuppe, Christoph, additional, Von Kriegsheim, Alex, additional, Kramann, Rafael, additional, Gnanapragasam, Vincent, additional, Warren, Anne Y., additional, Stewart, Grant D., additional, Erez, Ayelet, additional, Vanharanta, Sakari, additional, Saez-Rodriguez, Julio, additional, and Frezza, Christian, additional

Published
2021
Full Text
View/download PDF

15. Nrf2 is a central regulator of the metabolic landscape in macrophages and finetunes their inflammatory response

Author

Ryan, Dylan G., primary, Knatko, Elena V., additional, Casey, Alva, additional, Hukelmann, Jens L., additional, Brenes, Alejandro J., additional, Naidu, Sharadha Dayalan, additional, Higgins, Maureen, additional, Tronci, Laura, additional, Nikitopoulou, Efterpi, additional, O’Neill, Luke A.J., additional, Frezza, Christian, additional, Lamond, Angus I., additional, Abramov, Andrey Y., additional, Cantrell, Doreen A., additional, Murphy, Michael P., additional, and Dinkova-Kostova, Albena T., additional

Published
2021
Full Text
View/download PDF

16. Disruption of the TCA cycle reveals an ATF4-dependent integration of redox and amino acid metabolism

Author

Ryan, Dylan G., primary, Yang, Ming, additional, Prag, Hiran A., additional, Blanco, Giovanny Rodriguez, additional, Nikitopoulou, Efterpi, additional, Segarra-Mondejar, Marc, additional, Powell, Christopher A., additional, Young, Tim, additional, Burger, Nils, additional, Miljkovic, Jan Lj., additional, Minczuk, Michal, additional, Murphy, Michael P., additional, von Kriegsheim, Alexander, additional, and Frezza, Christian, additional

Published
2021
Full Text
View/download PDF

17. Disruption of the TCA cycle reveals an ATF4-dependent integration of redox and amino acid metabolism

Author

Ryan, Dylan Gerard, Yang, Ming, Prag, Hiran A., Blanco, Giovanny Rodriguez, Nikitopoulou, Efterpi, Segarra-Mondejar, Marc, Powell, Christopher A., Young, Tim, Burger, Nils, Miljkovic, Jan Lj, Minczuk, Michal, Murphy, Michael P., von Kriegsheim, Alex, Frezza, Christian, Ryan, Dylan Gerard, Yang, Ming, Prag, Hiran A., Blanco, Giovanny Rodriguez, Nikitopoulou, Efterpi, Segarra-Mondejar, Marc, Powell, Christopher A., Young, Tim, Burger, Nils, Miljkovic, Jan Lj, Minczuk, Michal, Murphy, Michael P., von Kriegsheim, Alex, and Frezza, Christian

Abstract

The Tricarboxylic Acid (TCA) Cycle is arguably the most critical metabolic cycle in physiology and exists as an essential interface coordinating cellular metabolism, bioenergetics, and redox homeostasis. Despite decades of research, a comprehensive investigation into the consequences of TCA cycle dysfunction remains elusive. Here, we targeted two TCA cycle enzymes, fumarate hydratase (FH) and succinate dehydrogenase (SDH), and combined metabolomics, transcriptomics, and proteomics analyses to fully appraise the consequences of TCA cycle inhibition (TCAi) in murine kidney epithelial cells. Our comparative approach shows that TCAi elicits a convergent rewiring of redox and amino acid metabolism dependent on the activation of ATF4 and the integrated stress response (ISR). Furthermore, we also uncover a divergent metabolic response, whereby acute FHi, but not SDHi, can maintain asparagine levels via reductive carboxylation and maintenance of cytosolic aspartate synthesis. Our work highlights an important interplay between the TCA cycle, redox biology, and amino acid homeostasis.

Published
2021

18. Succinate Anaplerosis Has an Onco-Driving Potential in Prostate Cancer Cells

Author

Sant’Anna-Silva, Ana Carolina B., primary, Perez-Valencia, Juan A., additional, Sciacovelli, Marco, additional, Lalou, Claude, additional, Sarlak, Saharnaz, additional, Tronci, Laura, additional, Nikitopoulou, Efterpi, additional, Meszaros, Andras T., additional, Frezza, Christian, additional, Rossignol, Rodrigue, additional, Gnaiger, Erich, additional, and Klocker, Helmut, additional

Published
2021
Full Text
View/download PDF

19. Nrf2 is a Central Regulator of the Metabolic Landscape in Macrophages and Finetunes Their Inflammatory Response

Author

Ryan, Dylan Gerard, primary, Knatko, Elena V., additional, Casey, Alva, additional, Hukelmann, Jens L., additional, Brenes, Alejandro J., additional, Dayalan Naidu, Sharadha, additional, Higgins, Maureen, additional, Tronci, Laura, additional, Nikitopoulou, Efterpi, additional, O’Neill, Luke A. J., additional, Frezza, Christian, additional, Lamond, Angus I., additional, Abramov, Andrey Y., additional, Cantrell, Doreen A., additional, Murphy, Michael P., additional, and Dinkova-Kostova, Albena, additional

Published
2021
Full Text
View/download PDF

20. Mechanism of succinate efflux upon reperfusion of the ischaemic heart

Author

Prag, Hiran A, primary, Gruszczyk, Anja V, additional, Huang, Margaret M, additional, Beach, Timothy E, additional, Young, Timothy, additional, Tronci, Laura, additional, Nikitopoulou, Efterpi, additional, Mulvey, John F, additional, Ascione, Raimondo, additional, Hadjihambi, Anna, additional, Shattock, Michael J, additional, Pellerin, Luc, additional, Saeb-Parsy, Kourosh, additional, Frezza, Christian, additional, James, Andrew M, additional, Krieg, Thomas, additional, Murphy, Michael P, additional, and Aksentijević, Dunja, additional

Published
2020
Full Text
View/download PDF

21. Lung Tumor Growth Promotion by Tobacco-Specific Nitrosamines Involves the β2-Adrenergic Receptors-Dependent Stimulation of Mitochondrial REDOX Signaling.

Author

Sarlak, Saharnaz, Lalou, Claude, Sant'Anna-Silva, Ana Carolina B., Mafhouf, Walid, De Luise, Monica, Rousseau, Benoît, Izotte, Julien, Claverol, Stéphane, Lacombe, Didier, Nikitopoulou, Efterpi, Yang, Ming, Oliveira, Marcus, Frezza, Christian, Gasparre, Giuseppe, Rezvani, Hamid Reza, Amoedo, Nivea Dias, and Rossignol, Rodrigue

Published
2022
Full Text
View/download PDF

22. Mechanism of succinate efflux upon reperfusion of the ischaemic heart.

Author

Prag, Hiran A, Gruszczyk, Anja V, Huang, Margaret M, Beach, Timothy E, Young, Timothy, Tronci, Laura, Nikitopoulou, Efterpi, Mulvey, John F, Ascione, Raimondo, Hadjihambi, Anna, Shattock, Michael J, Pellerin, Luc, Saeb-Parsy, Kourosh, Frezza, Christian, James, Andrew M, Krieg, Thomas, Murphy, Michael P, and Aksentijević, Dunja

Subjects
REPERFUSION, MONOCARBOXYLATE transporters, CORONARY circulation, REACTIVE oxygen species, HEART
Abstract

Aims  Succinate accumulates several-fold in the ischaemic heart and is then rapidly oxidized upon reperfusion, contributing to reactive oxygen species production by mitochondria. In addition, a significant amount of the accumulated succinate is released from the heart into the circulation at reperfusion, potentially activating the G-protein-coupled succinate receptor (SUCNR1). However, the factors that determine the proportion of succinate oxidation or release, and the mechanism of this release, are not known. Methods and results  To address these questions, we assessed the fate of accumulated succinate upon reperfusion of anoxic cardiomyocytes, and of the ischaemic heart both ex vivo and in vivo. The release of accumulated succinate was selective and was enhanced by acidification of the intracellular milieu. Furthermore, pharmacological inhibition, or haploinsufficiency of the monocarboxylate transporter 1 (MCT1) significantly decreased succinate efflux from the reperfused heart. Conclusion  Succinate release upon reperfusion of the ischaemic heart is mediated by MCT1 and is facilitated by the acidification of the myocardium during ischaemia. These findings will allow the signalling interaction between succinate released from reperfused ischaemic myocardium and SUCNR1 to be explored. [ABSTRACT FROM AUTHOR]

Published
2021
Full Text
View/download PDF

23. Succinate Anaplerosis Has an Onco-Driving Potential in Prostate Cancer Cells.

Author

Sant'Anna-Silva, Ana Carolina B., Perez-Valencia, Juan A., Sciacovelli, Marco, Lalou, Claude, Sarlak, Saharnaz, Tronci, Laura, Nikitopoulou, Efterpi, Meszaros, Andras T., Frezza, Christian, Rossignol, Rodrigue, Gnaiger, Erich, Klocker, Helmut, Kofler, Barbara, and Arsenian-Henriksson, Marie

Subjects
METABOLOMICS, OXYGEN consumption, SIGNAL peptides, MITOCHONDRIA, MEMBRANE transport proteins, CELL lines, PROSTATE tumors, METABOLITES, PHOSPHORYLATION
Abstract

Simple Summary: Depending on the availability of nutrients and increased metabolic demands, tumor cells rearrange their metabolism to survive and, ultimately, proliferate. Here, the authors investigated the effect of succinate, a metabolite of the mitochondrial citric acid cycle, on malignant and non-malignant prostate cells. They analyzed uptake through membrane transporters and intracellular accumulation, which subsequently fuels metabolism and enhances oncogenic properties of the tumor cells. The findings shed light to the metabolic adaptations that prostate tumor cells undergo, providing a better understanding of metabolic rewiring and strategies for therapeutic intervention. Tumor cells display metabolic alterations when compared to non-transformed cells. These characteristics are crucial for tumor development, maintenance and survival providing energy supplies and molecular precursors. Anaplerosis is the property of replenishing the TCA cycle, the hub of carbon metabolism, participating in the biosynthesis of precursors for building blocks or signaling molecules. In advanced prostate cancer, an upshift of succinate-driven oxidative phosphorylation via mitochondrial Complex II was reported. Here, using untargeted metabolomics, we found succinate accumulation mainly in malignant cells and an anaplerotic effect contributing to biosynthesis, amino acid, and carbon metabolism. Succinate also stimulated oxygen consumption. Malignant prostate cells displayed higher mitochondrial affinity for succinate when compared to non-malignant prostate cells and the succinate-driven accumulation of metabolites induced expression of mitochondrial complex subunits and their activities. Moreover, extracellular succinate stimulated migration, invasion, and colony formation. Several enzymes linked to accumulated metabolites in the malignant cells were found upregulated in tumor tissue datasets, particularly NME1 and SHMT2 mRNA expression. High expression of the two genes was associated with shorter disease-free survival in prostate cancer cohorts. Moreover, in-vitro expression of both genes was enhanced in prostate cancer cells upon succinate stimulation. In conclusion, the data indicate that uptake of succinate from the tumor environment has an anaplerotic effect that enhances the malignant potential of prostate cancer cells. [ABSTRACT FROM AUTHOR]

Published
2021
Full Text
View/download PDF

24. Succinate accumulation drives ischaemia-reperfusion injury during organ transplantation

Author

Martin, Jack L, Costa, Ana SH, Gruszczyk, Anja V, Beach, Timothy E, Allen, Fay M, Prag, Hiran A, Hinchy, Elizabeth C, Mahbubani, Krishnaa, Hamed, Mazin, Tronci, Laura, Nikitopoulou, Efterpi, James, Andrew M, Krieg, Thomas, Robinson, Alan J, Huang, Margaret M, Caldwell, Stuart T, Logan, Angela, Pala, Laura, Hartley, Richard C, Frezza, Christian, Saeb-Parsy, Kourosh, and Murphy, Michael P

Subjects
Mice, Swine, Reperfusion Injury, Succinic Acid, Animals, Humans, Organ Transplantation, 3. Good health
Abstract

During heart transplantation, storage in cold preservation solution is thought to protect the organ by slowing metabolism; by providing osmotic support; and by minimising ischaemia-reperfusion (IR) injury upon transplantation into the recipient1,2. Despite its widespread use our understanding of the metabolic changes prevented by cold storage and how warm ischaemia leads to damage is surprisingly poor. Here, we compare the metabolic changes during warm ischaemia (WI) and cold ischaemia (CI) in hearts from mouse, pig, and human. We identify common metabolic alterations during WI and those affected by CI, thereby elucidating mechanisms underlying the benefits of CI, and how WI causes damage. Succinate accumulation is a major feature within ischaemic hearts across species, and CI slows succinate generation, thereby reducing tissue damage upon reperfusion caused by the production of mitochondrial reactive oxygen species (ROS)3,4. Importantly, the inevitable periods of WI during organ procurement lead to the accumulation of damaging levels of succinate during transplantation, despite cooling organs as rapidly as possible. This damage is ameliorated by metabolic inhibitors that prevent succinate accumulation and oxidation. Our findings suggest how WI and CI contribute to transplant outcome and indicate new therapies for improving the quality of transplanted organs.

25. Bone Marrow Mesenchymal Stem Cells Support Acute Myeloid Leukemia Bioenergetics and Enhance Antioxidant Defense and Escape from Chemotherapy

Author

Forte, Dorian, García-Fernández, María, Sánchez-Aguilera, Abel, Stavropoulou, Vaia, Fielding, Claire, Martín-Pérez, Daniel, López, Juan Antonio, Costa, Ana SH, Tronci, Laura, Nikitopoulou, Efterpi, Barber, Michael, Gallipoli, Paolo, Marando, Ludovica, Fernández De Castillejo, Carlos López, Tzankov, Alexandar, Dietmann, Sabine, Cavo, Michele, Catani, Lucia, Curti, Antonio, Vázquez, Jesús, Frezza, Christian, Huntly, Brian J, Schwaller, Juerg, and Méndez-Ferrer, Simón

Subjects
Male, antioxidant, Antineoplastic Agents, acute myeloid leukemia, chemotherapy, Antioxidants, Mice, Bone Marrow, hemic and lymphatic diseases, Animals, Humans, glutathione, neoplasms, TCA cycle, Cells, Cultured, bone marrow mesenchymal stem cells, hematopoietic stem cell niche, metabolic adaptation, Mesenchymal Stem Cells, Middle Aged, OXPHOS, microenvironment, 3. Good health, Mice, Inbred C57BL, Leukemia, Myeloid, Acute, Female, Energy Metabolism
Abstract

Like normal hematopoietic stem cells, leukemic stem cells depend on their bone marrow (BM) microenvironment for survival, but the underlying mechanisms remain largely unknown. We have studied the contribution of nestin+ BM mesenchymal stem cells (BMSCs) to MLL-AF9-driven acute myeloid leukemia (AML) development and chemoresistance in vivo. Unlike bulk stroma, nestin+ BMSC numbers are not reduced in AML, but their function changes to support AML cells, at the expense of non-mutated hematopoietic stem cells (HSCs). Nestin+ cell depletion delays leukemogenesis in primary AML mice and selectively decreases AML, but not normal, cells in chimeric mice. Nestin+ BMSCs support survival and chemotherapy relapse of AML through increased oxidative phosphorylation, tricarboxylic acid (TCA) cycle activity, and glutathione (GSH)-mediated antioxidant defense. Therefore, AML cells co-opt energy sources and antioxidant defense mechanisms from BMSCs to survive chemotherapy.

26. Lung Tumor Growth Promotion by Tobacco-Specific Nitrosamines Involves the β2-Adrenergic Receptors-Dependent Stimulation of Mitochondrial REDOX Signaling

Author

Julien Izotte, Efterpi Nikitopoulou, Christian Frezza, Claude Lalou, Hamid Reza Rezvani, Stéphane Claverol, Rodrigue Rossignol, Saharnaz Sarlak, Monica De Luise, Ming Yang, Walid Mahfouf, Nivea Dias Amoedo, Benoit Rousseau, Marcus F. Oliveira, Didier Lacombe, Guiseppe Gasparre, Ana Carolina Bastos Sant'Anna-Silva, Sarlak, Saharnaz, Lalou, Claude, Sant'Anna-Silva, Ana Carolina B, Mafhouf, Walid, De Luise, Monica, Rousseau, Benoît, Izotte, Julien, Claverol, Stéphane, Lacombe, Didier, Nikitopoulou, Efterpi, Yang, Ming, Oliveira, Marcu, Frezza, Christian, Gasparre, Giuseppe, Rezvani, Hamid Reza, Amoedo, Nivea Dia, and Rossignol, Rodrigue

Subjects
Proteomics, Lung Neoplasms, Nitrosamines, Physiology, Clinical Biochemistry, Mitochondrion, medicine.disease_cause, Biochemistry, tobacco, lung, medicine, Humans, cancer, Tobacco-specific nitrosamines, Lung cancer, Molecular Biology, General Environmental Science, Chemistry, Cancer, bioenergetic, Cell Biology, TFAM, medicine.disease, Receptors, Adrenergic, mitochondria, Mitochondrial biogenesis, redox, Cancer research, Carcinogens, General Earth and Planetary Sciences, Signal transduction, Carcinogenesis, Oxidation-Reduction, Signal Transduction
Abstract

Aims: Lung cancer is the leading cause of cancer death worldwide, and tobacco smoking is a recognized major risk factor for lung tumor development. We analyzed the effect of tobacco-specific nitrosamines (TSNAs) on human lung adenocarcinoma metabolic reprogramming, an emergent hallmark of carcinogenesis. Results: A series of in vitro and in vivo bioenergetic, proteomic, metabolomic, and tumor biology studies were performed to analyze changes in lung cancer cell metabolism and the consequences for hallmarks of cancer, including tumor growth, cancer cell invasion, and redox signaling. The findings revealed that nicotine-derived nitrosamine ketone (NNK) stimulates mitochondrial function and promotes lung tumor growth in vivo. These malignant properties were acquired from the induction of mitochondrial biogenesis induced by the upregulation and activation of the beta-2 adrenergic receptors (β2-AR)-cholinergic receptor nicotinic alpha 7 subunit (CHRNAα7)-dependent nitrosamine canonical signaling pathway. The observed NNK metabolic effects were mediated by TFAM overexpression and revealed a key role for mitochondrial reactive oxygen species and Annexin A1 in tumor growth promotion. Conversely, ectopic expression of the mitochondrial antioxidant enzyme manganese superoxide dismutase rescued the reprogramming and malignant metabolic effects of exposure to NNK and overexpression of TFAM, underlining the link between NNK and mitochondrial redox signaling in lung cancer. Innovation: Our findings describe the metabolic changes caused by NNK in a mechanistic framework for understanding how cigarette smoking causes lung cancer. Conclusion: Mitochondria play a role in the promotion of lung cancer induced by tobacco-specific nitrosamines. Antioxid. Redox Signal. 36, 525-549.

Published
2022

Catalog

Books, media, physical & digital resources
See catalog results