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© 1999 American Heart Association, Inc.
Mini Review |
Nitric Oxide as a Bifunctional Regulator of Apoptosis
From the Department of Surgery (Y.-M.K., C.A.B., T.R.B.), University of Pittsburgh, Pittsburgh, Pa; Department of Molecular and Cellular Biology (Y.-M.K.), College of Medicine, Kangwon National University, Chunchon, Kanwon-do, Korea.
Correspondence to Timothy R. Billiar, MD, Watson Professor of Surgery, University of Pittsburgh Medical Center, A1010-Presbyterian University Hospital, Pittsburgh, PA 15213.
Key Words: nitric oxide • apoptosis • caspase • cGMP • peroxynitrite
It was inevitable that important relationships between two of the most intensely studied topics in biomedical research, apoptosis and nitric oxide (NO), would become apparent. Apoptosis is essential to normal development as well as physiological cell turnover. Although apoptosis in excess can manifest as tissue damage, a failure to undergo apoptosis constitutes pathological cellular overgrowth. It is now evident that NO and its reaction products can either promote or prevent apoptosis in a multitude of settings. The ubiquitous distribution of the NO synthases and the remarkable diffusibility and diverse chemical reactivity of NO in biological systems make this molecule unique among the regulators of apoptosis. Understanding the factors that govern the consequences of NO exposure on cell viability and identifying the conditions in which NO regulation of apoptosis contribute to pathology are topics of considerable interest and potential importance. In this article, we will review the recent observations on NO as a regulator of apoptosis.
Apoptosis, or programmed cell death, is distinguished from
lytic or necrotic cell death by specific biochemical and structural
events (see recent review in Reference 11 ). Apoptogenic signals trigger
cell-specific signaling pathways, including protease activation,
followed by the appearance of morphological changes characteristic of
cells undergoing apoptosis, including condensation of nuclei
and cytoplasm, blebbing of the cytoplasmic membranes, and finally
fragmentation into apoptotic bodies that are phagocytosed by
neighboring cells. The elucidation of the signaling events in
apoptosis is occurring at a rapid pace and includes the
identification of the key roles of cysteine proteases
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