Dysregulation of glutathione synthesis during cholestasis in mice: molecular mechanisms and therapeutic implications.

ABSTRACT:

Unlabelled

Glutathione (GSH) provides important antioxidant defense and regulates multiple critical processes including fibrogenesis. There are conflicting literature studies regarding changes in GSH during cholestasis. Here we examined changes in the GSH synthetic enzymes during bile duct ligation (BDL) in mice and how treatment with ursodeoxycholic acid (UDCA) and/or S-adenosylmethionine (SAMe) affects the expression of these enzymes and liver injury. The hepatic expression of glutamate-cysteine ligase (GCL) subunits and GSH synthase (GS) increased transiently after BDL but fell to 50% of baseline by 2 weeks. Nuclear factor-erythroid 2-related factor 2 (Nrf2) trans-activates gene expression by way of the antioxidant response element (ARE), which controls the expression of all thr

SUBMITTER: Yang H 

PROVIDER: S-EPMC2692579 | biostudies-literature | 2009 Jun

REPOSITORIES: biostudies-literature