title: Insulin protects apoptotic cardiomyocytes from hypoxia/reoxygenation injury through the sphingosine kinase/sphingosine 1-phosphate axis.
abstract: OBJECTIVE
  Experimental and clinical studies have shown that administration of insulin during reperfusion is cardioprotective, but the mechanisms underlying this effect are still unknown. In this study, the ability of insulin to protect apoptotic cardiomyocytes from hypoxia/reoxygenation injury using the sphingosine kinase/sphingosine 1-phosphate axis was investigated.
  
  
  RESULTS
  Rat cardiomyocytes were isolated and subjected to hypoxia and reoxygenation. [γ-32P] ATP was used to assess sphingosine kinase activity. Insulin was found to increase sphingosine kinase activity. Immunocytochemistry and Western blot analysis showed changes in the subcellular location of sphingosine kinase 1 from cytosol to the membrane in cardiomyocytes. Insulin caused cardiomyocytes to accumulate of S1P in a dose-dependent manner. FRET efficiency showed that insulin also transactivates the S1P1 receptor. TUNEL staining showed that administration of insulin during reoxygenation could to reduce the rate of reoxygenation-induced apoptosis, which is a requirement for SphK 1 activity. It also reduced the rate of activation of the S1P receptor and inhibited hypoxia/reoxygenation-induced cell death in cardiomyocytes.
  
  
  CONCLUSIONS
  The sphingosine kinase 1/sphingosine 1-phosphate/S1P receptor axis is one pathway through which insulin protects rat cardiomyocytes from apoptosis induced by hypoxia/reoxygenation injury.
authors.affiliation: College of Basic Medical Science, Jiujiang University, Jiujiang, China ; Key Laboratory of Jiangxi for the Systems Bio-medicine, Jiujiang, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Yu
authors.affiliation: College of Basic Medical Science, Jiujiang University, Jiujiang, China ; Key Laboratory of Jiangxi for the Systems Bio-medicine, Jiujiang, China.
authors.forename: Xiangxin
authors.initials: X
authors.lastname: Che
authors.affiliation: College of Basic Medical Science, Jiujiang University, Jiujiang, China ; Key Laboratory of Jiangxi for the Systems Bio-medicine, Jiujiang, China.
authors.forename: Xiaoyuan
authors.initials: X
authors.lastname: Xu
authors.affiliation: College of Basic Medical Science, Jiujiang University, Jiujiang, China.
authors.forename: Meirong
authors.initials: M
authors.lastname: Zheng
authors.affiliation: College of Basic Medical Science, Jiujiang University, Jiujiang, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: College of Basic Medical Science, Jiujiang University, Jiujiang, China.
authors.forename: Wei
authors.initials: W
authors.lastname: He
authors.affiliation: College of Basic Medical Science, Jiujiang University, Jiujiang, China ; Key Laboratory of Jiangxi for the Systems Bio-medicine, Jiujiang, China.
authors.forename: Jingmou
authors.initials: J
authors.lastname: Yu
authors.affiliation: College of Basic Medical Science, Jiujiang University, Jiujiang, China ; Key Laboratory of Jiangxi for the Systems Bio-medicine, Jiujiang, China.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Xiong
authors.affiliation: Key Laboratory of Jiangxi for the Systems Bio-medicine, Jiujiang, China.
authors.forename: Weidong
authors.initials: W
authors.lastname: Li
mesh_terms: D000818:Animals; D015687:Cell Hypoxia / Q000502:physiology; D002478:Cells, Cultured; D020287:In Situ Nick-End Labeling; D007328:Insulin / Q000494:pharmacology*; D008246:Lysophospholipids / Q000378:metabolism*; D015428:Myocardial Reperfusion Injury / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism*; D051381:Rats; D049349:Receptors, Lysosphingolipid / Q000378:metabolism; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000378:metabolism; D000099157:Sphingosine Kinase
chemical_list: D007328:Insulin; D008246:Lysophospholipids; D017853:Phosphotransferases (Alcohol Group Acceptor); D049349:Receptors, Lysosphingolipid; D013110:Sphingosine; D000099157:Sphingosine Kinase; C060506:sphingosine 1-phosphate