[KSCI] Korea Science Citation Index Service

http://dx.doi.org/10.5483/BMBRep.2013.46.1.037

Heat shock protein 90β inhibits apoptosis of intestinal epithelial cells induced by hypoxia through stabilizing phosphorylated Akt

Zhang, Shuai (Institute of Burn Research, Southwest Hospital, State Key Laboratory of Trauma, Burns and Combined Injury, Third Military Medical University)
Sun, Yong (Institute of Burn Research, Southwest Hospital, State Key Laboratory of Trauma, Burns and Combined Injury, Third Military Medical University)
Yuan, Zhiqiang (Institute of Burn Research, Southwest Hospital, State Key Laboratory of Trauma, Burns and Combined Injury, Third Military Medical University)
Li, Ying (Institute of Burn Research, Southwest Hospital, State Key Laboratory of Trauma, Burns and Combined Injury, Third Military Medical University)
Li, Xiaolu (Institute of Burn Research, Southwest Hospital, State Key Laboratory of Trauma, Burns and Combined Injury, Third Military Medical University)
Gong, Zhenyu (Institute of Burn Research, Southwest Hospital, State Key Laboratory of Trauma, Burns and Combined Injury, Third Military Medical University)
Peng, Yizhi (Institute of Burn Research, Southwest Hospital, State Key Laboratory of Trauma, Burns and Combined Injury, Third Military Medical University)

Publication Information

BMB Reports / v.46, no.1, 2013 , pp. 47-52 More about this Journal

Abstract

Intestinal epithelial cell (IEC) apoptosis induced by hypoxia compromise intestinal epithelium barrier function. Both Akt and Hsp90 have cytoprotective function. However, the specific role of Akt and $Hsp90{\beta}$ in IEC apoptosis induced by hypoxia has not been explored. We confirmed that hypoxia-induced apoptosis was reduced by $Hsp90{\beta}$ overexpression but enhanced by decreasing $Hsp90{\beta}$ expression. $Hsp90{\beta}$ overexpression enhanced BAD phosphorylation and thus reduced mitochondrial release of cytochrome C. Reducing $Hsp90{\beta}$ expression had opposite effects. The protective effect of $Hsp90{\beta}$ against apoptosis was negated by LY294002, an Akt inhibitor. Further study showed that Akt phosphorylation was enhanced by $Hsp90{\beta}$ , which was not due to the activation of upstream PI3K and PDK1 but because of stabilization of pAkt via direct interaction between $Hsp90{\beta}$ and pAkt. These results demonstrate that $Hsp90{\beta}$ may play a significant role in protecting IECs from hypoxia-induced apoptosis via stabilizing pAkt to phosphorylate BAD and reduce cytochrome C release.

Keywords

Apoptosis; Caco2 cells; Hypoxia; Intestinal epithelial cell; PI3K/Akt signaling pathway;

Citations & Related Records

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