OBJECTIVE: To evaluate the functional requirement of signal transducer and activator of transcription-3 (STAT-3) in cardiac myocyte tolerance to ischemia (I) and in classical preconditioning. METHODS: Cardiac myocyte STAT-3 was depleted in mice using Cre-lox p technology. Isolated cardiomyocytes from wild-type (WT) and STAT-3-deficient mice were evaluated for viability following simulated ischemia (SI; 26 h). Cardiomyocytes were then preconditioned by exposure to transient simulated ischemia or via the administration of preconditioning mimetics (100 microM adenosine, 100 microM diazoxide and 0.5 ng ml(-1) TNFalpha, individually and in combination) prior to index ischemia. To evaluate the effect of cardiac myocyte depletion of STAT-3 in the context of the intact heart, these experiments were performed in isolated perfused Langendorff heart preparations which were exposed to an index insult of 30-min global ischemia and 45-min reperfusion. Ischemic preconditioning was achieved by subjecting the hearts to four cycles of 5-min ischemia followed by 5-min reperfusion prior to index ischemia. Infarct size was measured following reperfusion. RESULTS: Cell viability was diminished equally in wild-type and STAT-3-depleted cardiomyocytes. In contrast, ischemic and pharmacological preconditioning protected wild-type cardiomyocytes but not STAT-3-deficient cardiomyocytes. These results were mirrored in the intact heart. CONCLUSION: The depletion of functional STAT-3 does not modulate tolerance to ischemic injury in cardiomyocytes. This signaling molecule, however, is crucial for the ischemic and all the tested pharmacological preconditioning programs.
OBJECTIVE: To evaluate the functional requirement of signal transducer and activator of transcription-3 (STAT-3) in cardiac myocyte tolerance to ischemia (I) and in classical preconditioning. METHODS: Cardiac myocyte STAT-3 was depleted in mice using Cre-lox p technology. Isolated cardiomyocytes from wild-type (WT) and STAT-3-deficient mice were evaluated for viability following simulated ischemia (SI; 26 h). Cardiomyocytes were then preconditioned by exposure to transient simulated ischemia or via the administration of preconditioning mimetics (100 microM adenosine, 100 microM diazoxide and 0.5 ng ml(-1) TNFalpha, individually and in combination) prior to index ischemia. To evaluate the effect of cardiac myocyte depletion of STAT-3 in the context of the intact heart, these experiments were performed in isolated perfused Langendorff heart preparations which were exposed to an index insult of 30-min global ischemia and 45-min reperfusion. Ischemic preconditioning was achieved by subjecting the hearts to four cycles of 5-min ischemia followed by 5-min reperfusion prior to index ischemia. Infarct size was measured following reperfusion. RESULTS: Cell viability was diminished equally in wild-type and STAT-3-depleted cardiomyocytes. In contrast, ischemic and pharmacological preconditioning protected wild-type cardiomyocytes but not STAT-3-deficient cardiomyocytes. These results were mirrored in the intact heart. CONCLUSION: The depletion of functional STAT-3 does not modulate tolerance to ischemic injury in cardiomyocytes. This signaling molecule, however, is crucial for the ischemic and all the tested pharmacological preconditioning programs.
Authors: Christopher C T Smith; Richard A Dixon; Abigail M Wynne; Louise Theodorou; Sang-Ging Ong; Sapna Subrayan; Sean M Davidson; Derek J Hausenloy; Derek M Yellon Journal: Am J Physiol Heart Circ Physiol Date: 2010-07-23 Impact factor: 4.733
Authors: Andrew P Wojtovich; William R Urciuoli; Shampa Chatterjee; Aron B Fisher; Keith Nehrke; Paul S Brookes Journal: Am J Physiol Heart Circ Physiol Date: 2013-04-12 Impact factor: 4.733
Authors: Seán P Barry; Paul A Townsend; James McCormick; Richard A Knight; Tiziano M Scarabelli; David S Latchman; Anastasis Stephanou Journal: Biochem Biophys Res Commun Date: 2009-05-18 Impact factor: 3.575