Cited by 19Nitric Oxide and Endothelin EffectsRedox biology and oxidative stressHemoglobin structure and function

The Role of Reactive Oxygen and Nitrogen Species in the Expression and Splicing of Nitric Oxide Receptor

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Sharina, Iraida G., Martin, Emil·2017·Antioxidants & Redox Signaling

Abstract

Significance: 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. Critical Issues: 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. Future Directions: 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.

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Authors
Sharina, I. G., & Martin, E.
Affiliations
  • The University of Texas Health Science Center at Houston (US)
  • Nazarbayev University (KZ)
Corresponding author
  • Sharina, Iraida G.
  • Martin, Emil
Venue
Antioxidants & Redox Signaling
Published
2017-01
Volume
26
Issue
3
Pages
122-136
ISSN
  • 1523-0864 (ISSN-L)
  • 1557-7716
OpenAlex
W2342294805
Cited by
19
References
142
Citations by year
2025: 3 · 2024: 1 · 2023: 4 · 2022: 1 · 2021: 1 · 2020: 1 · 2019: 2 · 2018: 4 · 2017: 1 · 2016: 1
FWCI
0.31
Type
journal article
Language
en
Open access
Locations
  • Antioxidants and Redox Signaling (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Nazarbayev University Repository (Nazarbayev University) (submittedVersion)
Funders
  • American Heart Association
  • National Heart, Lung, and Blood Institute (R01HL088128)
Topics
  • Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hemoglobin structure and function
Keywords
soluble guanylate cyclase, nitric oxide signaling, reactive oxygen species, reactive nitrogen species, oxidative stress, alternative splicing, splice variants, nitrosation, mRNA stability, compensatory mechanisms, vascular disease
MeSH terms
Soluble Guanylyl Cyclase, Animals, Gene Expression Regulation, Humans, Hydrogen Peroxide, Nitrogen, Oxidation-Reduction, Oxygen, RNA Splicing, Signal Transduction, Reactive Oxygen Species, Alternative Splicing, Oxidative Stress, Reactive Nitrogen Species

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