کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2533285 | 1559050 | 2010 | 9 صفحه PDF | دانلود رایگان |
Histone deacetylase (HDAC) inhibitors have recently been reported to have possible reno-protective effects in the last few years. In this study, we found that tricostatin A (TSA), an HDAC inhibitor, prevented transforming growth factor β1 (TGF-β1)-induced apoptosis in cultured human renal proximal tubular epithelial cells (RPTECs). TGF-β1-induced apoptosis via the activation of both caspase-8 and caspase-9 but did not activate the Fas receptor and did not alter Bcl-2 or Bax protein expression. TSA prevented TGF-β1-induced apoptosis and the activation of caspase-8 and caspase-9 in RPTECs but did not inhibit the TGF-β1-induced phosphorylation of Smad3 and p38 mitogen-activated protein kinase (MAPK). However, TSA inhibited the TGF-β1-induced phosphorylation of extracellular signal regulated kinase (ERK), and the MAPK/ERK kinase inhibitor U0126, which specifically inhibits ERK, also prevented TGF-β1-induced apoptosis. Our results show, for the first time, that TSA inhibits TGF-β1-induced ERK activation and overrides pro-apoptotic signals like Smad3 and p38 in human RPTECs.
Journal: European Journal of Pharmacology - Volume 642, Issues 1–3, 10 September 2010, Pages 28–36