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بیوشیمی مولکولی و سلولی 2013
جزئیات رویداد
همایش ، رویداد ، ژورنال
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  • hypoxia induces connexin 43 dysregulation by modulating matrix metalloproteinases via mapk signaling

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    • تاریخ ارائه: 1392/07/24
    • تاریخ انتشار در تی پی بین: 1392/07/24
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     connexin 43 (cx43) is a major structural protein found in the gap junctions of the ventricular myocardium and a major determinant of its electrical properties. the effects of matrix metalloproteinases (mmps), the mitogen-activated protein kinase (mapk) signaling pathway, transcription factor nf-kb, and activator protein-1 (ap-1)/c-jun on the regulation of cx43 gene expression in h9c2 cardiomyocytes were assessed. the mapk signaling pathway (mek/erk1/2 and pi3k) and transcription factors nf-kb and ap-1/c-jun were inhibited, then cx43 expression was assessed using western blot analysis, and mmp-9 activity was assessed using gelatin zymography. hypoxia decreased the cx43 protein level by approximately 30–50 %. doxycycline (10 μg/ml), an inhibitor of mmp, markedly attenuated the hypoxia-induced downregulation of cx43 protein expression at 6 h. the hypoxia-induced decrease in cx43 protein expression was significantly reversed by u0126 (10 μm), a mek/erk1/2 inhibitor, at 6 and 12 h; ly294002 (30 μm), a pi3k inhibitor, downregulated cx43 expression. hypoxia-induced mmp-9 activation was inhibited by treatment with ly294002, u0126, and, most especially, u0126. jsh-23 (30 μm), an nf-kb inhibitor, and sp600125 (10 μm), an ap-1/c-jun inhibitor, attenuated the loss of cx43. these results suggest that mapk signaling and the activities nf-kb and mmps play an important roles in the regulation of cx43 expression.

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