Cocaine- and amphetamine-regulated transcript peptide increases mitochondrial respiratory chain complex II activity and protects against oxygen-glucose deprivation in neurons.

Abstract The mechanisms of ischemic stroke, a main cause of disability and death, are complicated. Ischemic stroke results from the interaction of various factors including oxidative stress, a key pathological mechanism that plays an important role during the acute stage of ischemic brain injury. This study demonstrated that cocaine- and amphetamine-regulated transcript (CART) peptide, specifically CART 55–102 , increased the survival rate, but decreased the mortality of neurons exposed to oxygen–glucose deprivation (OGD), in a dose-dependent manner. The above-mentioned effects of CART 55–102 were most significant at 0.4 nM. These results indicated that CART 55–102 suppressed neurotoxicity and enhanced neuronal survival after oxygen–glucose deprivation. CART 55–102 (0.4 nM) significantly diminished reactive oxygen species levels and markedly increased the activity of mitochondrial respiratory chain complex II in oxygen–glucose deprived neurons. In summary, CART 55–102 suppressed oxidative stress in oxygen–glucose deprived neurons, possibly through elevating the activity of mitochondrial respiratory chain complex II. This result provides evidence for the development of CART 55–102 as an antioxidant drug.