Acute activation of acid ceramidase affects cytokine-induced cytotoxicity in rat islet β-cells

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• 作者：Qun Zhu ; Xiaohong Shan ; Heng Miao ; Yibing Lu ; Jiarong Xu ; Na You ; Chao Liu ; Duan-fang Liao ; Junfei Jin
• 关键词：Acid ceramidase ; Cytokine ; β ; -Cell ; Apoptosis ; Diabetes
• 刊名：FEBS Letters
• 出版年：2009
• 出版时间：18 June 2009
• 年：2009
• 卷：583
• 期：12
• 页码：2136-2141
• 全文大小：335 K

文摘

Ceramidase hydrolyzes ceramide and produces sphingosine as a substrate of sphingosine kinase (SPHK), which transforms sphingosine to sphingosine-1-phosphate. It has been reported that cytokines elicit SPHK activation in rat β-cells. As a sphingosine provider, ceramidase should also be activated. In our previous work, we showed that the increase in mRNA and protein levels in cytokine-treated INS-1 rat β-cells resulted in chronic activation of neutral ceramidase. Here we found that acid ceramidase (AC) is activated by cytokines at an early stage via tyrosine phosphorylation. In addition, basal AC activity was first detected in INS-1 cells and isolated rat islets, and cytokine-induced cell growth was significantly repressed when AC was pharmacologically inhibited.