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(Circulation Research. 2002;90:1237.)
© 2002 American Heart Association, Inc.

Editorials

Preventing Apoptosis With Thioredoxin

ASK Me How

Nanette H. Bishopric, Keith A. Webster

From the Departments of Pharmacology (N.H.B., K.A.W.) and Medicine (N.H.B.), University of Miami School of Medicine, Miami, Fla.

Correspondence to Nanette H. Bishopric, MD, FACC, Associate Professor of Pharmacology and Medicine, University of Miami School of Medicine, PO Box 016189 (R-189), Miami, FL 33101. E-mail n.bishopric@miami.edu

Key Words: reactive oxygen species • apoptosis signal-regulating kinase 1 • thioredoxin

An extract of the first 250 words of the full text is provided, because this article has no abstract.

Reactive oxygen species (ROS) are critical signaling molecules in eukaryotic cells, regulating growth, survival, and death pathways. High concentrations of ROS are cytotoxic, but low concentrations can promote growth and activate critical signal pathways in many cell types.¹ In the cardiovascular system, significant amounts of ROS are generated as byproducts of mitochondrial metabolism and may increase to toxic levels in the myocardium during and after periods of reduced blood flow. In addition, a number of extracellular peptide hormones are able to increase the production of ROS through receptor-mediated stimulation of membrane-bound NADPH oxidase.^2,3 The hypertrophic effects of angiotensin II⁴ and more recently other G protein–coupled receptor (GPCR) agonists⁵ have been shown to involve the generation of ROS through this mechanism. In addition, many apoptotic stresses in the cardiac myocyte, including ischemia-reperfusion and high concentrations of NO, signal through ROS. Oxidative stress is a central component of the mitochondrial permeability transition in cardiac myocytes, and the latter seems to underlie most pathologically relevant examples of cardiac myocyte apoptosis in vivo.⁶ Consequently, a clear understanding of the relationship between myocardial growth and apoptosis signaling will require a better understanding of the intracellular signals that respond to ROS.

In this issue of Circulation Research, Liu and Min⁷ shed light on a fascinating redox-sensitive mechanism that can generate both apoptotic and hypertrophic signals in the cardiovascular system. Apoptosis signal-regulating kinase 1 (ASK1), a member of the mitogen-activated protein kinase kinase kinase (MAP3K) family, is an upstream activator of p38 MAP kinases and c-Jun . . . [Full Text of this Article]

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