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Insulin protects apoptotic cardiomyocytes from hypoxia/reoxygenation injury through the sphingosine kinase/sphingosine 1-phosphate axis
- Source :
- PLoS ONE, Vol 8, Iss 12, p e80644 (2013), PLoS ONE
- Publication Year :
- 2013
- Publisher :
- Public Library of Science (PLoS), 2013.
-
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. Methods and 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. Conclusion 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.
- Subjects :
- Programmed cell death
medicine.medical_treatment
Sphingosine kinase
lcsh:Medicine
Myocardial Reperfusion Injury
chemistry.chemical_compound
Sphingosine
medicine
In Situ Nick-End Labeling
Animals
Insulin
Myocytes, Cardiac
Sphingosine-1-phosphate
lcsh:Science
Cells, Cultured
Multidisciplinary
TUNEL assay
biology
lcsh:R
Molecular biology
Cell Hypoxia
Cell biology
Rats
Phosphotransferases (Alcohol Group Acceptor)
Receptors, Lysosphingolipid
Sphingosine kinase 1
chemistry
Apoptosis
biology.protein
lcsh:Q
Lysophospholipids
Research Article
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 8
- Issue :
- 12
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....236663da816a73aadaec3ea95853c456