The role of mitochondria-mediated intrinsic death pathway in gingerdione derivative I6-induced neuronal apoptosis

Chia Ho Lin, Po See Chen, Sheng Chu Kuo, Li Jiau Huang, Po Wu Gean, Ted H. Chiu

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Neuronal death induced by I6 displayed apoptotic characteristics but the precise mechanism has not been fully elucidated. In the present studies, I6 at 24. h after intraperitoneal administration significantly decreased the density of surviving neurons and increased caspase-3 activity in frontal cortex, suggesting that peripherally administered I6 may cross BBB to induce CNS toxicity. In rat embryonic primary cortical cells, I6-induced reduction of mitochondrial viability and neuronal apoptosis was inhibited by vitamin E. In addition, I6-induced reactive oxygen species (ROS) caused the disruption of mitochondria membrane potential (MMP), the release of cytochrome c, the activation of caspase-9 and caspase-3, and cleavage of poly(ADP-ribose) polymerase (PARP), resulting in activation of mitochondrial-mediated intrinsic death pathway. Pre-treatment with antioxidant vitamin E or N-acetylcysteine (NAC) completely abolished the I6-induced generation of ROS, loss of MMP, release of cytochrome c, activation of caspase-9 and caspase-3, and cleavage of PARP. Carbonyl cyanide p-(trifluoromethoxy)phenylhydrazone (FCCP), a mitochondrial uncoupler, significantly reduced I6-induced neuronal death as well as caspase-3 activation and PARP cleavage. These results suggest that I6 induces neuronal death by promoting intracellular ROS production to cause a loss of MMP that result in release of cytochrome c and activation of mitochondria-mediated intrinsic death pathway.

Original languageEnglish
Pages (from-to)1073-1081
Number of pages9
JournalFood and Chemical Toxicology
Volume50
Issue number3-4
DOIs
Publication statusPublished - 2012 Mar 1

All Science Journal Classification (ASJC) codes

  • Food Science
  • Toxicology

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