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Changes in HSP70 and P53 expression are related to the pattern of electromechanical alterations in rat cardiomyocytes during simulated ischemia. Mol Cell Biochem 2001 Apr;220(1-2):77-86

Date

07/14/2001

Pubmed ID

11451386

DOI

10.1023/a:1010832731491

Scopus ID

2-s2.0-0034993602 (requires institutional sign-in at Scopus site)   10 Citations

Abstract

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.

Author List

Laubriet A, Fantini E, Assem M, Cordelet C, Teyssier JR, Athias P, Rochette L

Author

Mahfoud Assem PharmD Associate Professor in the School of Pharmacy Administration department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Blotting, Western
Cells, Cultured
Cyclin-Dependent Kinase Inhibitor p21
Cyclins
Electrophysiology
Genes, p53
HSP70 Heat-Shock Proteins
Ischemia
Kinetics
Myocardium
RNA, Messenger
Rats
Rats, Wistar
Reverse Transcriptase Polymerase Chain Reaction
Stress, Physiological
Tumor Suppressor Protein p53