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NO and superoxide: Opposite ends of the seesaw in cardiac contractility

Year: 2004

Type: article

Abstract: The discovery of superoxide dismutase by McCord and Fridovich (1) ushered in a new area of biology wherein free radicals had to be factored into the biology of animals and plants. The free radical species of oxygen, the superoxide anion radical, has become the focus of thousands of studies. In medicine, the number of disease processes that have been linked to overexposure to oxidants or a failure to defend against them is vast, including pathologies as diverse as neurodegeneration, sepsis, atherosclerosis, and arthritis. The NO free radical and its redox partners, the nitrosonium and nitroxide ions, have been similarly painted with broad negative brushes (2). More recently, NO has been recognized for its role in normal physiology, arising in part from its ability to act as a signal through regulation of guanylate cyclase (3) and to S -nitrosylate cysteinyl residues of proteins and peptides (3). In a recent issue of PNAS, we witnessed the emergence of a new paradigm wherein the interplay between different highly reactive species allows for complex and fast regulation of cellular processes whose disruption has potentially serious pathological consequences (4). Research from the Hare laboratory (5) has shown that the different isoforms of NO synthase (NOS) are involved in controlling different aspects of cardiac contractility. However, Khan et al. (4) present simple and clear studies that describe a new aspect to the paradigm of NO control that has broad application beyond the realm of contractility. Khan et al . show that the neuronal isoform of NOS (nNOS) and the superoxide-generating enzyme xanthine oxidoreductase (XOR) are in physical proximity in the sarcoplasmic reticulum (SR) of the cardiac myocytes of mice. Earlier studies have shown that superoxide production within cardiac myocytes has a potentially important signaling role (6). Furthermore, disruption of this signaling is involved in the …

Source: Proceedings of the National Academy of Sciences

DOI: 10.1073/pnas.0405859101

Authors: Joseph Bonaventura, Andrew Gow

Institutions: National Institutes of Health, Children's Hospital of Philadelphia, Duke Medical Center, University of Puerto Rico-Mayaguez, University of Pennsylvania

Language: English

Topic: Nitric Oxide and Endothelin Effects

Subfield: Physiology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: green

Funders: National Institutes of Health, National Center for Research Resources