Protective effect of creatine against inhibition by methylglyoxal of mitochondrial respiration of cardiac cells

Previous publications from our laboratory have shown that methylglyoxal inhibits mitochondrial respiration of malignant and cardiac cells, but it has no effect on mitochondrial respiration of other normal cells [Biswas, Ray, Misra, Dutta and Ray (1997) Biochem. J. 323, 343-348; Ray, Biswas and Ray (...

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Bibliographic Details
Published in:Biochemical journal 2003-06, Vol.372 (Pt 2), p.661-669
Main Authors: Roy, Soumya Sinha, Biswas, Swati, Ray, Manju, Ray, Subhankar
Format: Article
Language:English
Subjects:
Animals
Carcinoma, Ehrlich Tumor - metabolism
Carcinoma, Ehrlich Tumor - pathology
Carcinoma, Ehrlich Tumor - prevention & control
Cardiotonic Agents - pharmacology
Cell Respiration - drug effects
Chickens
Creatine - metabolism
Creatine - pharmacology
Creatine Kinase - antagonists & inhibitors
Creatine Kinase - metabolism
Creatine Kinase, Mitochondrial Form
Creatinine - pharmacology
Dinitrofluorobenzene - pharmacology
Dose-Response Relationship, Drug
Glutathione Disulfide - metabolism
Glutathione Disulfide - pharmacology
Glycolysis
Goats
Heart - drug effects
Isoenzymes - antagonists & inhibitors
Isoenzymes - metabolism
Lactoylglutathione Lyase - metabolism
Mercaptoethanol - pharmacology
Mice
Mitochondria, Heart - drug effects
Mitochondria, Heart - metabolism
Mitochondria, Muscle - drug effects
Mitochondria, Muscle - metabolism
Oxygen Consumption - drug effects
Phosphocreatine - pharmacology
Pyruvaldehyde - metabolism
Pyruvaldehyde - pharmacology
Rats
Tumor Cells, Cultured - drug effects
Tumor Cells, Cultured - metabolism
Urea - pharmacology
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Summary:Previous publications from our laboratory have shown that methylglyoxal inhibits mitochondrial respiration of malignant and cardiac cells, but it has no effect on mitochondrial respiration of other normal cells [Biswas, Ray, Misra, Dutta and Ray (1997) Biochem. J. 323, 343-348; Ray, Biswas and Ray (1997) Mol. Cell. Biochem. 171, 95-103]. However, this inhibitory effect of methylglyoxal is not significant in cardiac tissue slices. Moreover, post-mitochondrial supernatant (PMS) of cardiac cells could almost completely protect the mitochondrial respiration against the inhibitory effect of methylglyoxal. A systematic search indicated that creatine present in cardiac cells is responsible for this protective effect. Glutathione has also some protective effect. However, creatine phosphate, creatinine, urea, glutathione disulphide and beta-mercaptoethanol have no protective effect. The inhibitory and protective effects of methylglyoxal and creatine respectively on cardiac mitochondrial respiration were studied with various concentrations of both methylglyoxal and creatine. Interestingly, neither creatine nor glutathione have any protective effect on the inhibition by methylglyoxal on the mitochondrial respiration of Ehrlich ascites carcinoma cells. The creatine and glutathione contents of several PMS, which were tested for the possible protective effect, were measured. The activities of two important enzymes, namely glyoxalase I and creatine kinase, which act upon glutathione plus methylglyoxal and creatine respectively, were also measured in different PMS. Whether mitochondrial creatine kinase had any role in the protective effect of creatine had also been investigated using 1-fluoro-2,4-dinitrobenzene, an inhibitor of creatine kinase. The differential effect of creatine on mitochondria of cardiac and malignant cells has been discussed with reference to the therapeutic potential of methylglyoxal.
ISSN:0264-6021
1470-8728
DOI:10.1042/bj20021576