title: Acute activation of acid ceramidase affects cytokine-induced cytotoxicity in rat islet beta-cells.
abstract: 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 beta-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 beta-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.
authors.affiliation: Department of Endocrinology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210011, PR China.
authors.forename: Qun
authors.initials: Q
authors.lastname: Zhu
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Shan
authors.forename: Heng
authors.initials: H
authors.lastname: Miao
authors.forename: Yibing
authors.initials: Y
authors.lastname: Lu
authors.forename: Jiarong
authors.initials: J
authors.lastname: Xu
authors.forename: Na
authors.initials: N
authors.lastname: You
authors.forename: Chao
authors.initials: C
authors.lastname: Liu
authors.forename: Duan-fang
authors.initials: DF
authors.lastname: Liao
authors.forename: Junfei
authors.initials: J
authors.lastname: Jin
mesh_terms: D055573:Acid Ceramidase / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000633:toxicity*; D017931:DNA Primers / Q000235:genetics; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000201:enzymology* / Q000473:pathology; D008297:Male; D010766:Phosphorylation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014443:Tyrosine / Q000737:chemistry
chemical_list: D016207:Cytokines; D017931:DNA Primers; D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D014443:Tyrosine; D055573:Acid Ceramidase; C526736:Asah1 protein, rat