렙틴 수용체가 형질 도입된 신경세포에서 ER Stress로 유도된 렙틴저항성에 대한 일산화탄소의 억제작용

서지정보

· 발행기관 : 고신대학교(의대) 고신대학교 의과대학 학술지
· 수록지 정보 : 고신대학교 의과대학 학술지 / 25권 / 1호 / 42 ~ 50페이지
· 저자명 : 김성주, 김택상, 류현열, 정헌택

초록

Background: It is well known that leptin is an important circulating signal for the inhibition of food intake and the gain of body weight. Accumulating data suggest that leptin resistance has been considered to be one of the main causes of obesity. However, the detailed mechanism of leptin resistance is not known yet. Recently, endoplasmic reticulum (ER) stress-induced unfolded protein response (UPR) is reported to be responsible for the leptin resistance. Materials & methods: Carbon monoxide (CO), a reaction product of the cytoprotective heme oxygenase (HO)-1, is anti-apoptotic in a variety of models of cellular injury. Exogenous CO activated Nrf2 through the phosphorylation of protein kinase R-like endoplasmic reticulum kinase (PERK), resulting in HO-1 expression. CO-induced activation of PERK was followed by the phosphorylation of eukaryotic translation initiation factor 2a and the expression of activating transcription factor 4. However, CO fails to induce X-box binding protein-1 expression and activating transcription factor 6 cleavage. CO prevented X-box binding protein-1 expression and activating transcription factor 6 cleavage induced by ER-stress inducer such as thasigargin (TG), tunicamycin (TM) and homocysteine. Results: In the present study, we hypothesized that exogenous CO might block the leptin resistance which is induced by UPR during ER stress. Thasigargin or tunicamycin was used to induce ER stress. The activation status of leptin signals were measured by western blotting analysis using a phospho-signal transducer and activation of transcription3 (STAT3) antibody. In this study, ER stress markedly inhibited leptin-induced STAT3 phosphorylation. Conculusion: These results suggest that ER stress induces leptin resistance and exogenous CO-induced phosphorylation of PERK branch reversed ER stress-induced leptin resistance. Moreover, CO releasing molecule (CORM) blocks the inhibition of leptin-induced STAT3 phosphorylation. Together, the pathological mechanism of leptin resistance could be ameliorated by the use of exogenous CO..

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