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Regulation of ER stress proteins by valproate: therapeutic implications
Author(s) -
Bown Christopher D,
Wang JunFeng,
Chen Biao,
Young L Trevor
Publication year - 2002
Publication title -
bipolar disorders
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.285
H-Index - 129
eISSN - 1399-5618
pISSN - 1398-5647
DOI - 10.1034/j.1399-5618.2002.t01-1-40201.x
Subject(s) - calreticulin , endoplasmic reticulum , unfolded protein response , neuroprotection , hippocampus , downregulation and upregulation , neuroscience , medicine , pharmacology , microbiology and biotechnology , chemistry , biology , gene , biochemistry
Objectives:This paper reviews results of our studies examining the regulation of endoplasmic reticulum (ER) stress proteins by valproate (VPA), and discusses the possible implications in bipolar disorder.
Methods: Our previous studies in the field are reviewed along with relevant literature.
Results: Using differential display PCR, we identified GRP78 as a VPA‐regulated gene in rat cerebral cortex. We also showed that other members of the ER stress proteins family, GRP94 and calreticulin, are also upregulated by VPA. Immunohistochemistry identified that ER stress proteins are increased in frontal and parietal cortex, as well as regions of the hippocampus in rat brain following chronic treatment with VPA.
Conclusions: Regulation of ER stress proteins by VPA may prove to be important to the mechanism of action of the drug. The neuroprotective role of these proteins may also prove to be involved in the pathophysiology of bipolar disorder.