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بیوشیمی مولکولی و سلولی 2013
جزئیات رویداد
همایش ، رویداد ، ژورنال
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  • interleukin-6 inhibition of peroxisome proliferator-activated receptor alpha expression is mediated by jak2- and pi3k-induced stat1/3 in hepg2 hepatocyte cells

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    • تاریخ ارائه: 1392/07/24
    • تاریخ انتشار در تی پی بین: 1392/07/24
    • تعداد بازدید: 885
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    • شماره تماس دبیرخانه رویداد: -
     interleukin-6 (il-6) is the major activator of the acute phase response (apr). one important regulator of il-6-activated apr is peroxisome proliferator-activated receptor alpha (pparα). currently, there is a growing interest in determining the role of pparα in regulating apr; however, studies on the molecular mechanisms and signaling pathways implicated in mediating the effects of il-6 on the expression of pparα are limited. we previously revealed that il-6 inhibits pparα gene expression through caat/enhancer-binding protein transcription factors in hepatocytes. in this study, we determined that stat1/3 was the direct downstream molecules that mediated the janus kinase 2 (jak2) and phosphatidylinositol-3 kinase (pi3k)/akt/mammalian target of rapamycin (mtor) signaling pathways in il-6-induced repression of pparα. treatment of cells with pharmacological inhibitors of jak2, pi3k, akt, and mtor attenuated the inhibitory effect of il-6 on pparα protein in a dose-dependent manner. these inhibitors also decreased the il-6-induced repression of pparα mrna expression and promoter activity. overexpression of stat1 and stat3 in hepg2 cells cotransfected with a reporter vector containing this pparα promoter region revealed that both the expression plasmids inhibited the il-6-induced repression of pparα promoter activity. in the presence of inhibitors of jak2 and mtor (ag490 and rapamycin, respectively), il-6-regulated protein expression and dna binding of stat1 and stat3 were either completely or partially inhibited simultaneously, and the il-6-induced repression of pparα protein and mrna was also inhibited. this study has unraveled novel pathways by which il-6 inhibits pparα gene transcription, involving the modulation of jak2/stat1–3 and pi3k/akt/mtor by inducing the binding of stat1 and stat3 to stat-binding sites on the pparα promoter. together, these findings represent a new model of il-6-induced suppression of pparα expression by inducing stat1 and stat3 phosphorylation and subsequent down-regulation of pparα mrna expression.

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