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

A dibenzoylmethane derivative protects dopaminergic neurons against both oxidative stress and endoplasmic reticulum stress. Research Abstract Details 

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A dibenzoylmethane derivative protects dopaminergic neurons against both oxidative stress and endoplasmic reticulum stress. Abstract Text:

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,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,

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.

A dibenzoylmethane derivative protects dopaminergic neurons against both oxidative stress and endoplasmic reticulum stress. Publishing Authors By Initials

K Takano,Y Kitao,Y Tabata,H Miura,K Sato,K Takuma,K Yamada,S Hibino,T Choshi,M Iinuma,H Suzuki,R Murakami,M Yamada,S Ogawa,O Hori,K Takano,Y Kitao,Y Tabata,H Miura,K Sato,K Takuma,K Yamada,S Hibino,T Choshi,M Iinuma,H Suzuki,R Murakami,M Yamada,S Ogawa,O Hori,

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A dibenzoylmethane derivative protects dopaminergic neurons against both oxidative stress and endoplasmic reticulum stress. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: American journal of physiology. Cell physiology

VOLUME: 293

Page Numbers: C1884-94

Journal Abbreviation: Am. J. Physiol., Cell Physiol.

ISSN: 0363-6143

DAY: 3

MONTH: 10

YEAR: 2007

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

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LANGUAGE: eng

NlmUniqueID: 100901225

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AFFILIATION: Dept. of Neuroanatomy, Kanazawa Univ. Graduate School of Medical Science, 13-1 Takara-Machi, Kanazawa City, Ishikawa, 920-8640, Japan. osamuh@nanat.m.kanazawa-u.ac.jp).

Country: United States

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