Acute activation of acid ceramidase affects cytokine-induced cytotoxicity in rat islet beta-cells.
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.
Zhu
Qun
Q
Department of Endocrinology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210011, PR China.
Shan
Xiaohong
X
Miao
Heng
H
Lu
Yibing
Y
Xu
Jiarong
J
You
Na
N
Liu
Chao
C
Liao
Duan-fang
DF
Jin
Junfei
J
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
D016207:Cytokines; D017931:DNA Primers; D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D014443:Tyrosine; D055573:Acid Ceramidase; C526736:Asah1 protein, rat