title: Differential inhibition/inactivation of mitochondrial complex I implicates its alteration in malignant cells.
abstract: Methylglyoxal strongly inhibited mitochondrial respiration of a wide variety of malignant tissues including sarcoma of mice, whereas no such significant effect was noted on mitochondrial respiration of normal tissues with the exception of cardiac cells. This inhibition by methylglyoxal was found to be at the level of mitochondrial complex I (NADH dehydrogenase) of the electron transport chain. L-Lactaldehyde, which is structurally and metabolically related to methylglyoxal, could protect against this inhibition. NADH dehydrogenase of submitochondrial particles of malignant and cardiac cells was inhibited by methylglyoxal. This enzyme of these cells was also inactivated by methylglyoxal. The possible involvement of lysine residue(s) for the activity of NADH dehydrogenase was also investigated by using lysine-specific reagents trinitrobenzenesulfonic acid (TNBS) and pyridoxal 5' phosphate (PP). Inactivation of NADH dehydrogenase by both TNBS and PP convincingly demonstrated the involvement of lysine residue(s) for the activity of the sarcoma and cardiac enzymes, whereas both TNBS and PP failed to inactivate the enzymes of skeletal muscle and liver. Together these studies demonstrate a specific effect of methylglyoxal on mitochondrial complex I of malignant cells and importantly some distinct alteration of this complex in cancer cells.
authors.affiliation: Department of Biological Chemistry, Indian Association for the Cultivation of Science, Jadavpur, Kolkata.
authors.forename: A
authors.initials: A
authors.lastname: Ghosh
authors.forename: S
authors.initials: S
authors.lastname: Bera
authors.forename: S
authors.initials: S
authors.lastname: Ghosal
authors.forename: S
authors.initials: S
authors.lastname: Ray
authors.forename: A
authors.initials: A
authors.lastname: Basu
authors.forename: M
authors.initials: M
authors.lastname: Ray
mesh_terms: D000328:Adult; D000368:Aged; D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D015536:Down-Regulation; D042967:Electron Transport Complex I / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology*; D009245:NADH Dehydrogenase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D009369:Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D011765:Pyruvaldehyde / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D055815:Young Adult
chemical_list: D000447:Aldehydes; C014634:lactaldehyde; D011765:Pyruvaldehyde; D009245:NADH Dehydrogenase; D042967:Electron Transport Complex I