期刊
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
卷 1821, 期 12, 页码 1453-1461出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbalip.2012.08.005
关键词
Acid sphingomyelinase; Ceramide; Caspase 5; HuR cleavage; Apoptosis
资金
- National Natural Science Foundation of China [81160066, 30972797]
- Science & Technology Planning Project of Guangxi Province [1140003-79]
- Jiangsu Provincial Natural Science Foundation [BK2011861]
- Science &Technology Planning Project of Guilin City [20110119-1-8]
- Scientific Research Foundation for Returned Scholars, Ministry of Education of China [jyb2010-01]
- Open Fund of Medical Scientific Research Center of Guangxi Medical University [KFJJ2010-49, KY2011063]
- Key Project of Medical Research Foundation, Department of Public Health, Guangxi Province, China [2011006]
A previous data showed that the hypoxia mimetic compound CoCl2 induced cleavage of HuR and subsequent apoptosis in human oral cancer cells. We also previously demonstrated that exposure of NT-2 human neuronal precursor cells to hypoxia resulted in changes in sphingolipid levels and apoptosis. Since it is known that CoCl2 induces cleavage of HuR, we investigated whether there is a link between HuR cleavage and the observed sphingolipid changes in cells exposed to hypoxia, and whether this link is associated with the induction of apoptosis. Exposure of hepatocytes to direct hypoxia by means of a hypoxic chamber resulted in acid sphingomyelinase activation and ceramide elevation. The elevation in ceramide levels was associated with activation of caspase 5 and the subsequent cleavage of HuR and apoptotic cell death. These data raise the possibility that acid sphingomyelinase and caspase 5 are each potential targets for treating hypoxia (ischemia)-induced liver injury. (C) 2012 Elsevier B.V. All rights reserved.
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