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Published ahead of print on March 9, 2006, doi:10.1164/rccm.200510-1584PP
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American Journal of Respiratory and Critical Care Medicine Vol 173. pp. 1186-1193, (2006)
© 2006 American Thoracic Society
doi: 10.1164/rccm.200510-1584PP

Pulmonary Perspective

S-Nitrosothiol Signaling in Respiratory Biology

Benjamin Gaston, David Singel, Allan Doctor and Jonathan S. Stamler

Department of Pediatrics, University of Virginia Health System, Charlottesville, Virginia; Department of Chemistry, Montana State University, Boseman, Montana; and Pulmonary Medicine and Cell Biology, Duke University, Durham, North Carolina

Correspondence and requests for reprints should be addressed to Benjamin Gaston, M.D., Pediatric Respiratory Medicine, University of Virginia Health System, Box 800386, Charlottesville, VA 22908. E-mail: bmg3g{at}virginia.edu

ABSTRACT

Genetic and biochemical data demonstrate a pivotal role for S-nitrosothiols (SNOs) in mediating the actions of nitric oxide synthases (NOSs). SNOs serve to convey NO bioactivity and to regulate protein function. This understanding is of immediate interest to the pulmonary clinical and research communities. This article reviews the following: (1) biochemical and cellular evidence that SNOs in amino acids, peptides, and proteins elicit NOS-dependent signaling in the respiratory system and (2) studies that link SNO signaling to pulmonary medicine. SNO-mediated signaling is involved in the regulation of minute ventilation, ventilation–perfusion matching, pulmonary arterial pressure, basal airway tone, and respiratory and peripheral muscle function. Derangements in SNO signaling are implicated in many disorders relevant to pulmonary and critical care medicine, including apnea, hypoxemia, pulmonary hypertension, asthma, cystic fibrosis, pneumonia, and septic shock.

Key Words: asthma • cystic fibrosis • pulmonary hypertension • S-nitrosoglutathione • S-nitrosohemoglobin • S-nitrosylation




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