Melatonin inhibits neural apoptosis induced by homocysteine in hippocampus of rats via inhibition of cytochrome c translocation and caspase-3 activation and by regulating pro- and anti-apoptotic protein levels

Baydas G., Reiter R., Akbulut M., Tuzcu M., Tamer S.

NEUROSCIENCE, vol.135, no.3, pp.879-886, 2005 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 135 Issue: 3
  • Publication Date: 2005
  • Doi Number: 10.1016/j.neuroscience.2005.05.048
  • Journal Name: NEUROSCIENCE
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.879-886
  • Istanbul University Affiliated: Yes

Abstract

In the present study, we examined the molecular mechanism by which homocysteine causes neuronal cell apoptosis. We further investigated the mechanisms of melatonin's ability to reduce homocysteine-induced apoptosis. Consistent with its antioxidant properties, melatonin reduced homocysteine-induced lipid peroxidation and stimulated glutathione peroxidase enzyme activity in hippocampus of rats with hyperhomocysteinemia. Furthermore, melatonin treatment diminished cytochrome c release from mitochondria and reduced caspase 3 and caspase 9 activation induced by hyperhomocysteinemia. Chronic hyperhomocysteinemia also led to poly(ADP-ribose) polymerase cleavage and subsequently DNA fragmentation. Treatment with melatonin markedly inhibited poly(ADP-ribose) polymerase cleavage and reduced DNA damage. Hyperhomocysteinemia caused an elevation of pro-apoptotic Bax levels while reducing antiapoptotic protein, Bcl-2, levels. Daily administration of melatonin up-regulated Bcl-2 and down-regulated Bax levels. We propose that, in addition to its antioxidant properties, melatonin has the ability to protect neuronal cells against apoptosis mediated homocysteine neurotoxicity by modulating apoptosis-regulatory proteins in the hippocampus of rats. (c) 2005 IBRO. Published by Elsevier Ltd. All rights reserved.