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A protective role of selenoprotein S (SEPS1) against endoplasmic reticulum stress‐induced cytotoxicity and apoptosis in macrophages
Author(s) -
Kim KeeHong,
Skelton Joseph,
Walder Ken,
Gao Yuan,
Collier Greg,
Kissebah Ahmed
Publication year - 2006
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.20.4.a507
Subject(s) - unfolded protein response , endoplasmic reticulum , apoptosis , microbiology and biotechnology , macrophage , cytotoxicity , chemistry , downregulation and upregulation , biology , biochemistry , in vitro , gene
Macrophage apoptosis is a key feature of advanced atherosclerosis. Moreover, stress generated from the endoplasmic reticulum (ER) due to accumulation of free cholesterol in ER and activation of the unfolded protein response (UPR) in macrophage contributes to the development of macrophage apoptosis. We recently identified a novel ER resident protein SEPS1 whose putative function is related to ER stress and inflammatory responses in humans. In order to understand the role of SEPS1 in ER stress‐induced cellular dysfunction, here we examined the ER stress‐dependent regulation of SEPS1 expression and the consequence of SEPS1 overexpression in Raw 264.7 murine macrophages during ER stress. We demonstrate that various ER stress agents increased SEPS1 mRNA expression in Raw 264.7 cells. This is accompanied by ER stress‐dependent stimulation of SEPS1 level in a dose‐ and time‐dependent manner. We next examined the consequence of overexpression of SEPS1 in ER stress‐induced cytotoxicity and apoptosis. The overexpression of SEPS1 in Raw 264.7 cells protected cells against ER stress‐induced cytotoxicity and apoptosis. These results indicate a cytoprotective role of SEPS1 in macrophages during ER stress, resulting in an attenuation of ER stress‐induced apoptosis. Together out study implicates an important role for SEPS1 in regulating ER stress‐induced apoptosis and SEPS1 may be a novel target to promote macrophage survival.