Association of prohibitin-1 and 2 with oxidative stress in rats with renal interstitial fibrosis.

Prohibitins PHB1 and PHB2 are evolutionary conserved and pleiotropic proteins, which have been shown to be important factors in various cellular functions, including proliferation, tumour suppression, apoptosis, transcription, and mitochondrial protein folding. Recently, we demonstrated that down-regulation promoted renal interstitial fibrosis (RIF) in ureteral obstructed rats. Furthermore, the hypoxic conditions and oxidative stress have been implicated in obstruction-mediated renal disease. This study was performed to explore the association of PHBs with oxidative stress in a rat model of RIF. PHBs, the pro-fibrotic transforming growth factor-β1 (TGF-β1), and the extracellular matrix proteins collagen-IV (Col-IV) and fibronectin (FN) were evaluated, as were markers of oxidative stress [total reactive oxygen species (ROS), malondialdehyde (MDA)] and antioxidative capacity (superoxide dismutase, glutathione), and apoptosis. Our results showed a progressive increase in oxidative stress and concomitant decrease in antioxidants over a period of 4 weeks ureteral obstruction. Concomitantly, profibrotic components increased and PHB expression decreased. Overall, both PHBs were negatively correlated with the extent of observed fibrosis, TGF-β1, Col-IV, FN, ROS, MDA, and apoptosis.