KMID : 0624620130460010047
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BMB Reports 2013 Volume.46 No. 1 p.47 ~ p.52
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Heat shock protein 90¥â inhibits apoptosis of intestinal epithelial cells induced by hypoxia through stabilizing phosphorylated Akt
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Zhang Shuai
Sun Yong Yuan Zhiqiang Li Ying Li Xiaolu Gong Zhenyu Peng Yizhi
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Abstract
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Intestinal epithelial cell (IEC) apoptosis induced by hypoxia compromise intestinal epithelium barrier function. Both Akt and Hsp90 have cytoprotective function. However, the specific role ofAkt and Hsp90¥â in IEC apoptosis induced by hypoxia has not been explored. We confirmed thathypoxia-induced apoptosis was reduced by Hsp90¥â overexpression but enhanced by decreasing Hsp90¥â expression. Hsp90¥â overexpression enhanced BAD phosphorylation and thus reduced mitochondrial release of cytochrome C. Reducing Hsp90¥â expression had opposite effects. The protective effect of Hsp90¥â against apoptosis was negated by LY294002, an Akt inhibitor. Further study showed that Akt phosphorylation was enhanced by Hsp90¥â, which was not due to the activation of upstream PI3K and PDK1 but because of stabilization of pAkt via direct interaction between Hsp90¥â and pAkt. These results demonstrate that Hsp90¥â may play a significant role in protecting IECs from hypoxia-induced apoptosis via stabilizing pAkt to phosphorylate BAD and reduce cytochrome C release.
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KEYWORD
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Apoptosis, Caco2 cells, Hypoxia, Intestinal epithelial cell, PI3K/Akt signaling pathway
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