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Differential regulation of Bcl‐2, AP‐1 and NF‐κB on cardiomyocyte apoptosis during myocardial ischemic stress adaptation
Author(s) -
Maulik Nilanjana,
Goswami Shyamal,
Galang Nathaniel,
Das Dipak K.
Publication year - 1999
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(98)01719-0
Subject(s) - apoptosis , ischemia , downregulation and upregulation , dna fragmentation , transcription factor , chemistry , reperfusion injury , microbiology and biotechnology , medicine , biology , programmed cell death , biochemistry , gene
Acute ischemia followed by prolonged reperfusion has been shown to induce cardiomyocyte apoptosis. In this report, we demonstrate that myocardial adaptation to ischemia induced by repeated cyclic episodes of short‐term ischemia each followed by another short duration of reperfusion reduced cardiomyocyte apoptosis and DNA fragmentation. This was associated with the induction of the expression of Bcl‐2 mRNA and translocation and activation of NF‐κB. Another transcription factor, AP‐1, remained unaffected by repeated ischemia and reperfusion, but exhibited significant upregulation by a single episode of 30 min ischemia followed by 2 h of reperfusion. This activation of AP‐1 was inhibited by a scavenger of oxygen free radicals, DMTU. Thirty minutes ischemia and 120 min reperfusion downregulated the induction of the expression of Bcl‐2 mRNA, but moderately activated NF‐κB binding activity. This was associated with an increased number of apoptotic cells and DNA fragmentation in cardiomyocytes which were attenuated by DMTU. The results of this study indicate that Bcl‐2, AP‐1 and NF‐κB differentially regulate cardiomyocyte apoptosis mediated by acute ischemia and prolonged reperfusion.