β-Adrenergic Receptor–Stimulated Apoptosis in Cardiac Myocytes Is Mediated by Reactive Oxygen Species/c-Jun NH ₂ -Terminal Kinase–Dependent Activation of the Mitochondrial Pathway

Abstract

Stimulation of beta-adrenergic receptors (betaARs) causes apoptosis in adult rat ventricular myocytes (ARVMs). The role of reactive oxygen species (ROS) in mediating betaAR-stimulated apoptosis is not known. Stimulation of betaARs with norepinephrine (10 micromol/L) in the presence of prazosin (100 nmol/L) for 24 hours increased the number of apoptotic myocytes as determined by TUNEL staining by 3.6- fold. The superoxide dismutase/catalase mimetics Mn(III)tetrakis(1-methyl-4-pyridyl)porphyrin pentachloride (MnTMPyP; 10 micromol/L) and Euk-134 decreased betaAR-stimulated apoptosis by 89+/-6% and 76+/-10%, respectively. Infection with an adenovirus expressing catalase decreased betaAR-stimulated apoptosis by 82+/-15%. The mitochondrial permeability transition pore inhibitor bongkrekic acid (50 micromol/L) decreased betaAR-stimulated apoptosis by 76+/-8%, and the caspase inhibitor zVAD-fmk (25 micromol/L) decreased betaAR-stimulated apoptosis by 62+/-11%. betaAR-stimulated cytochrome c release was inhibited by MnTMPyP. betaAR stimulation caused c-Jun NH2-terminal kinase (JNK) activation, which was abolished by MnTMPyP. Transfection with an adenovirus expressing dominant-negative JNK inhibited betaAR-stimulated apoptosis by 81+/-12%, and the JNK inhibitor SP600125 inhibited both betaAR-stimulated apoptosis and cytochrome c release. Thus, betaAR-stimulated apoptosis in ARVMs involves ROS/JNK-dependent activation of the mitochondrial death pathway.

Tomato lycopene attenuates myocardial infarction induced by isoproterenol: Electrocardiographic, biochemical and anti–apoptotic study

“…Increased caspase-3 protease activity and DNA damage indicates cardiac apoptosis and necrosis in the present study. Study have reported that 毬 -AR stimulation by catecholamine induces cardiac apoptosis or/and necrosis [31] . It has been already reported that oxidative stress provoke DNA damage (DNA fragmentation and apoptosis) and treatment with antioxidants inhibit DNA fragmentation and apoptosis [32] .…”

“…The heart was transversely cut across the left ventricle to obtain slices no more than 0.1 cm in thickness. The heart slices were placed in the covered, darkened glass dish containing pre warmed (1%) TTC solution in phosphate buffer and the dish was incubated between 37-40 曟 for [30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45] min. the heart slices were turned over once or twice to make certain that it remains immersed and covered by 1 cm of the TTC solution.…”

Haemodynamic effects of levosimendan in advanced but stable chronic heart failure

“…Acute decompensated HF (ADHF) is the most common cause of hospitalization,3 and cardiogenic shock occurs in about 4% of ADHF admissions 4. Conventional inotropes improve haemodynamics and organ perfusion and relieve symptoms, but due to short half‐lives, they are limited to selected inpatients and outpatients with continuous infusions and are pro‐ischaemic, are pro‐arrhythmic, and may be associated with increased mortality 5, 6, 7, 8, 9…”

Small Heat-Shock Protein Hsp20 Attenuates β-Agonist–Mediated Cardiac Remodeling Through Apoptosis Signal–Regulating Kinase 1

“…8,9 The MAPKs, mainly including JNKs, p38 kinases, and extracellular signal-related kinase 1/2 (ERK1/2), have been implicated in the pro-and antiapoptotic effects of the enhanced ␤-adrenergic signaling pathway. 10,11 However, it is not currently clear whether increased sympathetic tone directly activates the MAPKs or whether regulation occurs upstream of these molecules.…”