title: The Role of Reactive Oxygen and Nitrogen Species in the Expression and Splicing of Nitric Oxide Receptor.
abstract: Nitric oxide (NO)-dependent signaling is critical to many cellular functions and physiological processes. Soluble guanylyl cyclase (sGC) acts as an NO receptor and mediates the majority of NO functions. The signaling between NO and sGC is strongly altered by reactive oxygen and nitrogen species. Recent Advances: Besides NO scavenging, sGC is affected by oxidation/loss of sGC heme, oxidation, or nitrosation of cysteine residues and phosphorylation. Apo-sGC or sGC containing oxidized heme is targeted for degradation. sGC transcription and the stability of sGC mRNA are also affected by oxidative stress.
  
  
  
  Studies cited in this review suggest the existence of compensatory processes that adapt cellular processes to diminished sGC function under conditions of short-term or moderate oxidative stress. Alternative splicing of sGC transcripts is discussed as a mechanism with the potential to both enhance and reduce sGC function. The expression of α1 isoform B, a functional and stable splice variant of human α1 sGC subunit, is proposed as one of such compensatory mechanisms. The expression of dysfunctional splice isoforms is discussed as a contributor to decreased sGC function in vascular disease.
  
  
  
  Targeting the process of sGC splicing may be an important approach to maintain the composition of sGC transcripts that are expressed in healthy tissues under normal conditions. Emerging new strategies that allow for targeted manipulations of RNA splicing offer opportunities to use this approach as a preventive measure and to control the composition of sGC splice isoforms. Rational management of expressed sGC splice forms may be a valuable complementary treatment strategy for existing sGC-directed therapies. Antioxid. Redox Signal. 26, 122-136.
authors.affiliation: 1 Division of Cardiology, Department of Internal Medicine, The University of Texas Health Science Center in Houston Medical School , Houston, Texas.
authors.forename: Iraida G
authors.initials: IG
authors.lastname: Sharina
authors.affiliation: 1 Division of Cardiology, Department of Internal Medicine, The University of Texas Health Science Center in Houston Medical School , Houston, Texas.|2 School of Science and Technology, Nazarbayev University , Astana, Kazakhstan .
authors.forename: Emil
authors.initials: E
authors.lastname: Martin
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D005786:Gene Expression Regulation; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D009584:Nitrogen / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010100:Oxygen / Q000378:metabolism; D012326:RNA Splicing; D026361:Reactive Nitrogen Species / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction; D000071756:Soluble Guanylyl Cyclase / Q000235:genetics* / Q000378:metabolism*
chemical_list: D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D000071756:Soluble Guanylyl Cyclase; D009584:Nitrogen; D010100:Oxygen
keywords: nitric oxide; oxidative stress; soluble guanylyl cyclase; splicing