Biochemical mechanism of GSH depletion induced by 1,2-dibromoethane in isolated rat liver mitochondria. Evidence of a GSH conjugation process.
HPLC measurements of GSH and GSSG levels in isolated rat liver mitochondria, on addition of 1,2-dibromoethane (DBE), revealed the presence of a glutathione (GSH)-conjugating pathway of DBE. This process required the structural integrity of the mitochondrial matrix and inner membrane complex and was inhibited by the uncouplers of oxidative phosphorylation, particularly 2,4-dinitrophenol. On the other hand it was not affected by the energetic state of the mitochondria, since other mitochondrial inhibitors like KCN and oligomycin did not have any effect on it. This process also did not require the involvement of mitochondrial inner membrane transport systems, based on the measurement of the mitochondrial transmembrane potential. The involvement of mitochondrial GSH-S-transferases, located either in the matrix or in the intermembrane space, is discussed.
Botti
B
B
Istituto di Patologia Generale, Univesità di Modena, Modena, Italy.
Ceccarelli
D
D
Tomasi
A
A
Vannini
V
V
Muscatello
U
U
Masini
A
A
D000818:Animals; D002273:Carcinogens / Q000494:pharmacology*; D004533:Egtazic Acid / Q000494:pharmacology; D015946:Ethylene Dibromide / Q000494:pharmacology*; D005978:Glutathione / Q000031:analogs & derivatives / Q000378:metabolism*; D019803:Glutathione Disulfide; D006842:Hydrocarbons, Brominated / Q000494:pharmacology*; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D014475:Uncoupling Agents / Q000494:pharmacology
D002273:Carcinogens; D006842:Hydrocarbons, Brominated; D014475:Uncoupling Agents; D015946:Ethylene Dibromide; D004533:Egtazic Acid; D005978:Glutathione; D019803:Glutathione Disulfide