Cited by 19Nitric Oxide and Endothelin EffectsHemoglobin structure and functionHeme Oxygenase-1 and Carbon Monoxide

Regulation of sGC via hsp90, Cellular Heme, sGC Agonists, and NO: New Pathways and Clinical Perspectives

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Ghosh, Arnab, Stuehr, Dennis J.·2017·Antioxidants & Redox Signaling

Abstract

Significance: Soluble guanylate cyclase (sGC) is an intracellular enzyme that plays a primary role in sensing nitric oxide (NO) and transducing its multiple signaling effects in mammals. Recent Advances: The chaperone heat shock protein 90 (hsp90) associates with signaling proteins in cells, including sGC, where it helps to drive heme insertion into the sGC-β1 subunit. This allows sGC-β1 to associate with a partner sGC-α1 subunit and mature into an NO-responsive active form. Critical Issues: In this article, we review evidence to date regarding the mechanisms that modulate sGC activity by a pathway where binding of hsp90 or sGC agonist to heme-free sGC dictates the assembly and fate of an active sGC heterodimer, both by NO and heme-dependent or heme-independent pathways. Future Directions: We discuss some therapeutic implications of the NO-sGC-hsp90 nexus and its potential as a marker of inflammatory disease. Antioxid. Redox Signal. 26, 182–190.

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Authors
Ghosh, A., & Stuehr, D. J.
Affiliations
Cleveland Clinic (US)
Venue
Antioxidants & Redox Signaling
Published
2017-02
Volume
26
Issue
4
Pages
182-190
ISSN
  • 1523-0864 (ISSN-L)
  • 1557-7716
OpenAlex
W2345818691
Cited by
19
References
99
Citations by year
2024: 1 · 2023: 2 · 2021: 2 · 2020: 3 · 2019: 2 · 2018: 5 · 2017: 4
FWCI
2.95
Type
journal article
Language
en
Open access
Locations
  • Antioxidants and Redox Signaling (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (HL081064)
  • National Heart, Lung, and Blood Institute (P01HL103453, P01HL081064, U10HL109250)
  • National Institute of General Medical Sciences (R01GM097041)
Topics
  • Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hemoglobin structure and function
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heme Oxygenase-1 and Carbon Monoxide
Keywords
soluble guanylate cyclase, HSP90, heme insertion, nitric oxide signaling, chaperone-mediated protein folding, therapeutic target
MeSH terms
Soluble Guanylyl Cyclase, Cytosol, Disease Susceptibility, Heme, Humans, Models, Biological, Models, Molecular, Nitric Oxide, Protein Binding, Protein Conformation, Signal Transduction, Biomarkers, HSP90 Heat-Shock Proteins, Nitric Oxide Synthase, Protein Multimerization, Eukaryota

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