S-adenosylmethionine induces mitochondrial dysfunction, permeability transition pore opening and redox imbalance in subcellular preparations of rat liver
| Autor: | Thabata Fernandes, Ângela Zanatta, Rafael Teixeira Ribeiro, Bianca Seminotti, Guilhian Leipnitz, Ana Cristina Roginski, Moacir Wajner, Kaleb Pinto Spannenberger, Lucas Henrique Rodrigues da Silva, Alexandre Umpierrez Amaral |
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| Rok vydání: | 2021 |
| Předmět: |
Male
Membrane potential S-Adenosylmethionine biology Physiology Chemistry Cell Biology Glutathione Adenosine kinase Mitochondrial Membrane Transport Proteins Aconitase Permeability Rats Cell biology Lipid peroxidation chemistry.chemical_compound Liver Lipid oxidation Mitochondrial permeability transition pore Cyclosporin a biology.protein Animals Rats Wistar Oxidation-Reduction |
| Zdroj: | Journal of Bioenergetics and Biomembranes. 53:525-539 |
| ISSN: | 1573-6881 0145-479X |
| Popis: | S-adenosylmethionine (AdoMet) predominantly accumulates in tissues and biological fluids of patients affected by liver dysmethylating diseases, particularly glycine N-methyltransferase, S-adenosylhomocysteine hydrolase and adenosine kinase deficiencies, as well as in some hepatic mtDNA depletion syndromes, whose pathogenesis of liver dysfunction is still poorly established. Therefore, in the present work, we investigated the effects of S-adenosylmethionine (AdoMet) on mitochondrial functions and redox homeostasis in rat liver. AdoMet decreased mitochondrial membrane potential and Ca2+ retention capacity, and these effects were fully prevented by cyclosporin A and ADP, indicating mitochondrial permeability transition (mPT) induction. It was also verified that the thiol-alkylating agent NEM prevented AdoMet-induced ΔΨm dissipation, implying a role for thiol oxidation in the mPT pore opening. AdoMet also increased ROS production and provoked protein and lipid oxidation. Furthermore, AdoMet reduced GSH levels and the activities of aconitase and α-ketoglutarate dehydrogenase. Free radical scavengers attenuated AdoMet effects on lipid peroxidation and GSH levels, supporting a role of ROS in these effects. It is therefore presumed that disturbance of mitochondrial functions associated with mPT and redox unbalance may represent relevant pathomechanisms of liver damage provoked by AdoMet in disorders in which this metabolite accumulates. |
| Databáze: | OpenAIRE |
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