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KMID : 0928520090190020161
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Korean Journal of Lipidology
2009 Volume.19 No. 2 p.161 ~ p.172
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CO Protects Hepatocytes from Apoptotic Endoplasmic Recticulum Stress Induced by Glucose Deprivation
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Min Zheng
Joe Yeon-Soo
Pae Hyun-ock
Chung Hun-Taeg
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Abstract
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Background: Carbon monoxide (CO), a reaction product of the cytoprotective heme oxygenase (HO)-1, has anti-apoptotic, anti-inflammatory, and anti-proliferative effects in a variety of models of cellular injury. Also, CO-mediated cytoprotective effects were induced by glucose deprivation. The decrease of glucose levels causes the transcriptional regulation of genes associated with endoplasmic reticulum (ER) stress response.
Methods and results: Murine embryonic liver BNL CL.2 cells and primary rat hepatocytes were cultured for detection of ER stress - induced apoptosis in glucose deprivation. Glucose deprivation caused unfolded protein responses (UPR) as phophorylation of PERK and eIF2α, expression of xbp-1, GRP78 and ATF-4, and cleavage of ATF-6 in time dependent manner just like well known ER stressor, thapsigargin. On 24 hours after glucose deprivation the cells showed the programmed cell death concomitant with the expression of CHOP. This cytotoxicity caused by glucose deprivation was inhibited by NO donor, sodium nitropruside (SNP), and the HO-1 inducer, hemin, and CO. Also HO-1 and CO prevented the apoptosis triggered by these ER inducers such as thapsigargin, tunicamycin and glucose deprivation. CO prevented glucose deprivation-induced apoptosis by suppressing CHOP express. CO inhibited the CHOP expression via p38 MAPK-dependent manner
Conclusions: HO-1 and CO system protects hepatocyte from glucose deprivation-induced cell death via the inhibition of CHOP expression in a p38 MAPK dependent fashion
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KEYWORD
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Cabon monoxide, Heme oxygenase-1, ER stress, Apoptosis
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