A dibenzoylmethane derivative protects dopaminergic neurons against both oxidative stress and endoplasmic reticulum stress

Katsura Takano, Yasuko Kitao, Yoshiyuki Tabata, Hikari Miura, Kosuke Sato, Kazuhiro Takuma, Kiyofumi Yamada, Satoshi Hibino, Tominari Choshi, Munekazu Iinuma, Hiroto Suzuki, Rika Murakami, Masashi Yamada, Satoshi Ogawa, Osamu Hori

Research output: Contribution to journalArticlepeer-review

45 Citations (Scopus)

Abstract

The enhancement of intracellular stresses such as oxidative stress and endoplasmic reticulum (ER) stress has been implicated in several neurodegenerative disorders including Parkinson's disease (PD). During a search for compounds that regulate ER stress, a dibenzoylmethane (DBM) derivative 14-26 (2,2′-dimethoxydibenzoylmethane) was identified as a novel neuroprotective agent. Analysis in SH-SY5Y cells and in PC12 cells revealed that the regulation of ER stress by 14-26 was associated with its anti-oxidative property. 14-26 prevented the production of reactive oxygen species (ROS) when the cells were exposed to oxidants such as hydrogen peroxide and 6-hydroxydopamine (6-OHDA) or an ER stressor brefeldin A (BFA). 14-26 also prevented ROS-induced damage in both the ER and the mitochondria, including the protein carbonylation in the microsome and the reduction of the mitochondrial membrane potential. Further examination disclosed the presence of the iron-chelating activity in 14-26. In vivo, 14-26 suppressed both oxidative stress and ER stress and prevented neuronal death in the substantia nigra pars compacta (SNpc) after injection of 6-OHDA in mice. These results suggest that 14-26 is an antioxidant that protects dopaminergic neurons against both oxidative stress and ER stress and could be a therapeutic candidate for the treatment of PD.

Original languageEnglish
Pages (from-to)C1884-C1894
JournalAmerican Journal of Physiology - Cell Physiology
Volume293
Issue number6
DOIs
Publication statusPublished - 12-2007
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cell Biology

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