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• W1970498090 abstract "Reactive oxygen species (ROS) play a crucial role in the pathophysiology of ischemic heart disease by causing cardiac dysfunction and cell death. Several redox-sensitive anti- and pro-apoptotic transcription factors including NFkappaB and AP-1 progressively and steadily increase in the heart as a function of the duration of ischemia and reperfusion. When the heart is preconditioned to ischemic stress by repeated short-term ischemia and reperfusion, NFkappaB remains high while AP-1 is lowered to almost baseline value. The anti-apoptotic gene Bcl-2 is downregulated in the ischemic/reperfused heart, while it is upregulated in the adapted myocardium. Cardioprotective abilities of the preconditioning are abolished when heart is pre-perfused with N-acetyl cysteine, a scavenger for ROS, suggesting the role of ROS in redox signaling. Mammalian heart is protected by several defense systems which include among others, redox-regulated protein, thioredoxin. Reperfusion of ischemic myocardium results in the downregulation of thioredoxin 1 (Trx 1) expression, which was upregulated in the preconditioned myocardium. The increased expression of Trx 1 is completely blocked with an inhibitor of Trx 1, CDDP, which also abolished cardioprotection afforded by ischemic adaptation. The cardioprotective role of Trx 1 is confirmed further with transgenic mouse hearts overexpressing Trx 1. The Trx 1 mouse hearts displayed significantly improved post-ischemic ventricular recovery and reduced myocardial infarct size and apoptosis as compared to the corresponding wild-type mouse hearts. Taken together, preconditioning appears to potentiate redox signaling, which converts the death signal into survival signal." @default.
• W1970498090 created "2016-06-24" @default.
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• W1970498090 date "2003-12-01" @default.
• W1970498090 modified "2023-10-15" @default.
• W1970498090 title "Preconditioning potentiates redox signaling and converts death signal into survival signal" @default.
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• W1970498090 doi "https://doi.org/10.1016/j.abb.2003.09.023" @default.
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