Troglitazone induces cytotoxicity in part by promoting the degradation of peroxisome proliferator-activated receptor γ co-activator-1α protein.

ABSTRACT:

Background and purpose

Troglitazone (Tro), rosiglitazone (Rosi) and pioglitazone (Pio) are anti-diabetic thiazolidinediones that function as ligands for peroxisome proliferator-activated receptor γ (PPARγ); however, Tro has been withdrawn from the market due to liver toxicity issues. Mitochondrial dysfunction induced by Tro has been suggested to be an important mechanism behind its cytotoxicity. Constitutively active nuclear hormone receptors, oestrogen-related receptor α and γ are thought to regulate mitochondrial mass and oxidative phosphorylation together with their co-activators PPARγ co-activator-1α and -1β (PGC-1α and PGC-1β). Hence, in this study, we investigated whether Tro affects the expression and activity levels of these regulators.

Experimental approach

Cellular

SUBMITTER: Liao X 

PROVIDER: S-EPMC2992894 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature