Lopimune-induced mitochondrial toxicity is attenuated by increased uncoupling protein-2 level in treated mouse hepatocytes

• DOI: 10.1042/bj20150195
• Publication Date: 2015-04-14T15:40:28Z
• Authors: Sara El Hoss; Georges M. Bahr; Karim S. Echtay
• Keywords: Bioenergetics; Mitochondrial ROS; Submitochondrial particle

Although the protease inhibitor (PI) Lopimune has proven to be effective, no studies have examined side effects of on mitochondrial bioenergetics in hepatocytes. The objective present study is evaluate respiration, production reactive oxygen species (ROS) and expression uncoupling protein-2 (UCP2) mouse hepatocytes following administration. Mitochondria were extracted from liver using differential centrifugation isolated by collagenase perfusion procedure. Mitochondrial respiration was measured a Rank Brothers electrode. ROS monitored flow cytometry 2',7'-dichlorofluorescin diacetate probe UCP2 protein detected Western blotting. We found that induced significant decrease approximately 30% respiratory control ratio (RCR) starting day 4 until 9 treatment. This due an increase state reflecting proton leak. State 2 3 respirations not affected. Moreover, significantly increased about 2-fold after 1 treatment decreased 3, returning resting level 5. Interestingly, which absent hepatocytes, expressed Our findings indicate Lopimune-induced leak, mediated UCP2, may represent response inhibit as negative feedback regulatory mechanism. These results imply potential involvement regulation oxidative stress add new insights into understanding toxicity PIs.