The role of acid sphingomyelinase and caspase 5 in hypoxia-induced HuR cleavage and subsequent apoptosis in hepatocytes.
A previous data showed that the hypoxia mimetic compound CoCl(2) 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 CoCl(2) 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.
Department of Hepatobiliary Surgery, Affiliated Hospital of Guilin Medical University, Guilin, 541001, Guangxi, People's Republic of China.
Qun
Q
Zhu
Lianku
L
Lin
Qi
Q
Cheng
Qing
Q
Xu
Jingmei
J
Zhang
Stephen
S
Tomlinson
Junfei
J
Jin
Xiaoping
X
Chen
Songqing
S
He
D017209:Apoptosis; D015153:Blotting, Western; D020169:Caspases / Q000235:genetics / Q000378:metabolism*; D015687:Cell Hypoxia; D002478:Cells, Cultured; D002518:Ceramides / Q000378:metabolism; D051959:ELAV Proteins / Q000378:metabolism*; D004789:Enzyme Activation; D015870:Gene Expression; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013108:Sphingomyelin Phosphodiesterase / Q000235:genetics / Q000378:metabolism*
D002518:Ceramides; D051959:ELAV Proteins; C112980:acid sphingomyelinase-1; D013108:Sphingomyelin Phosphodiesterase; C099217:CASP5 protein, human; D020169:Caspases