Glucose and its metabolites have distinct effects on the calcium-induced mitochondrial permeability transition
Language English Country Czech Republic Media print
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
21888832
PII: file/5586/FB2011A0015.pdf
Knihovny.cz E-resources
- MeSH
- Glucose metabolism pharmacology MeSH
- Glucosephosphates metabolism pharmacology MeSH
- Intracellular Membranes drug effects physiology MeSH
- Mitochondria, Liver drug effects physiology ultrastructure MeSH
- Rats MeSH
- Permeability drug effects MeSH
- Rats, Wistar MeSH
- Pyruvaldehyde pharmacology MeSH
- Reactive Oxygen Species metabolism MeSH
- Calcium metabolism pharmacology MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Glucose MeSH
- Glucosephosphates MeSH
- Pyruvaldehyde MeSH
- Reactive Oxygen Species MeSH
- Calcium MeSH
Mitochondrial production of reactive oxygen species (ROS) due to up-regulated glucose oxidation is thought to play a crucial, unifying role in the pathogenesis of chronic complications associated with diabetes mellitus. Mitochondrial permeability transition (MPT) is an interesting phenomenon involved in calcium signalling and cell death. We investigated the effects of glucose and several of its metabolites on calcium-induced MPT (measured as mitochondrial swelling) in isolated rat liver mitochondria. The presence of glucose, glucose 1-phosphate (both at 30 mM) or methylglyoxal (6 mM) significantly slowed calcium-induced mitochondrial swelling. Thirty mM glucose also resulted in a significant delay of MPT onset. In contrast, 30 mM fructose 6-phosphate accelerated swelling, whereas glucose 6-phosphate did not influence the MPT. The calcium binding potentials of the three hexose phosphates were tested and found similar. In vitro hydrogen peroxide production by mitochondria respiring on succinate in the presence of rotenone was independent of mitochondrial membrane potential and increased transiently during calcium-induced MPT. Inhibition of MPT with cyclosporine A resulted in decreased mitochondrial ROS production in response to calcium. In contrast, inhibition of MPT by methylglyoxal was accompanied by increased ROS production in response to calcium. In conclusion, we confirm that methylglyoxal is a potent inhibitor of MPT. In addition, high levels of glucose, glucose 1-phosphate and fructose 6-phosphate can also affect MPT. Methylglyoxal simultaneously inhibits MPT and increases mitochondrial ROS production in response to calcium. Our findings provide a novel context for the role of MPT in glucose sensing and the cellular toxicity caused by methylglyoxal.
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