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Endoplasmic Reticulum (ER) Stress inhibition via S‐methyl‐N, N‐diethylthiocarbamate sulfoxide (DETC‐MeSO) in Focal Cerebral Artery Occlusion in Rat
Author(s) -
MohammadGharibani Payam,
Modi Jigar,
Menzi Janet,
Prentice Howard,
Tao Rui,
Wu Jang Yen
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.672.4
Subject(s) - penumbra , neuroprotection , unfolded protein response , hsp70 , hsp27 , heat shock protein , endoplasmic reticulum , protein kinase b , chemistry , ischemia , medicine , endocrinology , pharmacology , microbiology and biotechnology , biology , signal transduction , biochemistry , gene
ER functions can be disturbed after excitotoxicity which leads to changes in calcium homeostasis. One approach for protecting neurons from excitotoxic damage is blocking of NMDA receptors with specific antagonists. We investigated the neuroprotective effect of DETC‐MeSO, a partial antagonist of NMDA receptors in the rat stroke model. Focal cerebral ischemia was induced by occlusion of the left middle cerebral artery for 2 hours. DETC‐MeSO (5.6 mg/kg) was administered subcutaneously for 4 days, then rats were sacrificed and infarct size in the left hemisphere was measured by TTC staining. Western Blotting on the core and the penumbra tissue of both hemispheres was done for analysis of the expression of key proteins involved in apoptosis (Bax, Bcl‐2), heat shock proteins (HSP27, HSP70), GRP78, ER stress markers (IRE1, PERK and ATF6 pathways) and p‐AKT. TTC staining showed that DETC‐MeSO can decrease the lesion volume size in the left hemisphere. Up‐regulation of Bcl‐2 to Bax ratio was seen in the core and the penumbra of treatment group. HSP27 and p‐AKT protein expression were increased in the core and the penumbra of treated group, while HSP70 and GRP78 protein expression showed no changes. Our data indicated that the administration of DETC‐MeSO can attenuate ER stress, mostly via IRE1 pathway mediated by down‐regulation of IRE1α, Ask1, JNK and GADD34 proteins and up‐regulation of Bcl‐2 protein. Grant Funding Source : Florida Department of Health