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

Brain Res. 2014 Sep 25:1582:107-13. doi: 10.1016/j.brainres.2014.07.043. Epub 2014 Aug 13.

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 CART55-102, 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 CART55-102 were most significant at 0.4nM. These results indicated that CART55-102 suppressed neurotoxicity and enhanced neuronal survival after oxygen-glucose deprivation. CART55-102 (0.4nM) significantly diminished reactive oxygen species levels and markedly increased the activity of mitochondrial respiratory chain complex II in oxygen-glucose deprived neurons. In summary, CART55-102 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 CART55-102 as an antioxidant drug.

Keywords: Cocaine- and amphetamine-regulated transcript peptides; Mitochondrial respiratory chain; Neuroprotection; Oxygen–glucose deprivation; Reactive oxygen species.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Death / drug effects
  • Cell Hypoxia / drug effects*
  • Cell Hypoxia / physiology
  • Cell Survival / drug effects
  • Cells, Cultured
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / physiology
  • Dose-Response Relationship, Drug
  • Electron Transport Complex II / metabolism*
  • Flow Cytometry
  • Glucose / deficiency*
  • Mice
  • Nerve Tissue Proteins / administration & dosage*
  • Neurons / drug effects*
  • Neurons / physiology
  • Neuroprotective Agents / administration & dosage*
  • Reactive Oxygen Species / metabolism

Substances

  • Nerve Tissue Proteins
  • Neuroprotective Agents
  • Reactive Oxygen Species
  • cocaine- and amphetamine-regulated transcript protein
  • Electron Transport Complex II
  • Glucose