Myocardial self-preservation: absence of heat shock factor activation and heat shock proteins 70 mRNA accumulation in the human heart during cardiac surgery.
Following myocardial ischemia, heat shock proteins (HSPs) have been found to be associated with a reduction in infarct size and enhanced postischemic functional recovery. Stress-induced regulation of the HSPs is mediated by the activation and binding of the heat shock transcription factor (HSF) to a specific DNA sequence located in front of all HSP genes, known as the heat shock element (HSE). To determine whether HSPs were induced in the human heart following the ischemic stress experienced during cardiac surgery, biopsies were performed of the right atrium at three sequential times: prior to establishing cardiopulmonary bypass; immediately after aortic declamping; and following termination of bypass. These samples from the atria of patients undergoing coronary bypass surgery were assessed for HSF activation using mobility shift gels, and analyzed for HSP 72 mRNA by Northern blot. Although a high level of the HSP 72 protein was noted at all intervals, no HSF activation was detected, nor was an accumulation of HSP 72 mRNA observed at any time during surgery. These data suggest that HSPs are not induced during cardiac surgery and that the high "constitutive" level of the HSP 72 protein detected in these hearts may not be secondary to an HSF-HSE interaction, but rather, the result of other transcription factors acting at alternative regions of the HSP 70 promoter.
McGrath
L B
LB
Department of Surgery, Deborah Heart and Lung Center, Browns Mills, NJ 08015, USA.
Locke
M
M
D000368:Aged; D015152:Blotting, Northern; D002315:Cardiopulmonary Bypass; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D004591:Electrophoresis, Polyacrylamide Gel; D018840:HSP70 Heat-Shock Proteins / Q000032:analysis / Q000096:biosynthesis*; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins / Q000096:biosynthesis*; D006801:Humans; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology*; D012333:RNA, Messenger / Q000032:analysis; D014157:Transcription Factors
D004268:DNA-Binding Proteins; D018840:HSP70 Heat-Shock Proteins; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins; D012333:RNA, Messenger; D014157:Transcription Factors