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Regulation of Respiration and Endothelial Gene Expression by S-Nitrosothiols in Health and Disease

Department of Pediatrics and Anesthesiology, University of Virginia Health System, Charlottesville, Virginia

Correspondence and requests for reprints should be addressed to Lisa A. Palmer, Ph.D., Department of Pediatrics, P.O. Box 801366, University of Virginia, Charlottesville, VA 22908. E-mail: lap5w{at}virginia.edu

ABSTRACT

The effects of nitric oxide (NO) are mediated by cyclic guanosine monophosphate (cGMP)-dependent and cGMP-independent processes. Most cGMP-independent effects are mediated by the actions of S-nitrosothiols (SNOs). SNOs have been shown to play a role in health and in disease. In studies performed in the mouse and rat, the ventilatory response to hypoxia is regulated in the nucleus tractus solitarius by SNOs exported from red blood cells. This may affect the treatment of respiratory distress in newborns and sleep apnea in adults. Likewise, SNOs have been shown to alter the stability and abundance of the transcription factor hypoxia inducible factor-1, altering the expression of hypoxia-regulated genes. Identification of the proteins involved in these signaling events will lead to new therapeutic approaches in the treatment of diseases characterized by limited oxygen availability.

Key Words: glutamyl transpeptidase • hypoxia inducible factor-1 • S-nitrosothiols