Document Detail


Sphingosine kinase and sphingosine 1-phosphate in the heart: a decade of progress.
MedLine Citation:
PMID:  22735359     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Activation of sphingosine kinase/sphingosine 1-phosphate (SK/S1P)-mediated signaling has emerged as a critical cardioprotective pathway in response to acute ischemia/reperfusion injury. S1P is released in both ischemic pre- and post-conditioning. Application of exogenous S1P to cultured cardiac myocytes subjected to hypoxia or treatment of isolated hearts either before ischemia or at the onset of reperfusion exerts prosurvival effects. Synthetic congeners of S1P such as FTY720 mimic these responses. Gene targeted mice null for the SK1 isoform whose hearts are subjected to ischemia/reperfusion injury exhibit increased infarct size and respond poorly either to ischemic pre- or postconditioning. Measurements of cardiac SK activity and S1P parallel these observations. Experiments in SK2 knockout mice have revealed that this isoform is necessary for survival in the heart. High density lipoprotein (HDL) is a major carrier of S1P, and studies of hearts in which selected S1P receptors have been inhibited implicate the S1P cargo of HDL in cardioprotection. Inhibition of S1P lyase, an endogenous enzyme that degrades S1P, also leads to cardioprotection. These observations have considerable relevance for future therapeutic approaches to acute and chronic myocardial injury. This article is part of a Special Issue entitled Advances in Lysophospholipid Research.
Authors:
Joel S Karliner
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Review     Date:  2012-06-23
Journal Detail:
Title:  Biochimica et biophysica acta     Volume:  1831     ISSN:  0006-3002     ISO Abbreviation:  Biochim. Biophys. Acta     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2012-11-06     Completed Date:  2013-06-12     Revised Date:  2014-01-10    
Medline Journal Info:
Nlm Unique ID:  0217513     Medline TA:  Biochim Biophys Acta     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  203-12     Citation Subset:  IM    
Copyright Information:
Published by Elsevier B.V.
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MeSH Terms
Descriptor/Qualifier:
Aldehyde-Lyases / metabolism
Animals
Cardiotonic Agents / metabolism
Humans
Lipoproteins, HDL / metabolism
Lysophospholipids / metabolism*
Myocardium / enzymology*
Phosphotransferases (Alcohol Group Acceptor) / metabolism*
Sphingosine / analogs & derivatives*,  metabolism
Grant Support
ID/Acronym/Agency:
1P01 HL68738/HL/NHLBI NIH HHS; P01 HL068738/HL/NHLBI NIH HHS; R01 HL090606/HL/NHLBI NIH HHS; R01 HL090606/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Cardiotonic Agents; 0/Lipoproteins, HDL; 0/Lysophospholipids; 26993-30-6/sphingosine 1-phosphate; EC 2.7.1.-/Phosphotransferases (Alcohol Group Acceptor); EC 2.7.1.-/sphingosine kinase; EC 4.1.2.-/Aldehyde-Lyases; EC 4.1.2.-/sphingosine 1-phosphate lyase (aldolase); NGZ37HRE42/Sphingosine
Comments/Corrections

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