Changes in HSP70 and P53 expression are related to the pattern of electromechanical alterations in rat cardiomyocytes during simulated ischemia.
The objective was to relate the response of the HSP70 and P53 genes to the cessation and the recovery of cardiac muscle cell functions when submitted to ischemia-reperfusion. We have measured the electromechanical activity, the released enzymes and HSP70 RNA and protein levels in cultured neonatal rat cardiomyocytes (CM) in a substrate-free, hypoxia-reoxygenation model of ischemia-reperfusion. In parallel the expression of the two genes P53 (the key apoptosis regulator gene) and P21/Waf1 (the P53 target gene) has been evaluated. The functional recovery during post-'ischemic' reoxygenation was associated with an overexpression of HSP70 and P53 lasting until the functional parameters reverted back to the normal, prehypoxic values. In contrast, extending the substrate-free hypoxic treatment worsens the dysfunction of the cardiac muscle cell and, in these conditions, reoxygenation failed to restore cell functions and to activate HSP70. Finally, in the conditions of reversible 'ischemic' cell injury, an early and transitory activation of P53 was associated with the functional recovering process of the CM submitted to simulated ischemia. These observations are suggestive of a contributive role of both HSP70 and P53 to a cytoprotective program activated by reoxygenation in post-'ischemic' CM.
Laubriet
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A
Laboratory of Cardiovascular Physiopathology and Pharmacology, Faculty of Medicine, University of Burgundy, Dijon, France.
Fantini
E
E
Assem
M
M
Cordelet
C
C
Teyssier
J R
JR
Athias
P
P
Rochette
L
L
D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000096:biosynthesis; D004594:Electrophysiology; D016158:Genes, p53 / Q000235:genetics; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis*; D007511:Ischemia; D007700:Kinetics; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013312:Stress, Physiological; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*
C493958:Cdkn1a protein, rat; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D018840:HSP70 Heat-Shock Proteins; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53