Regulation of sGC via hsp90, Cellular Heme, sGC Agonists, and NO: New Pathways and Clinical Perspectives
Open accessAbstract
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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The activity of sGC itself is compromised in a number of pathological conditions.
“Apart from changes in NO levels or downstream signaling, the activity of sGC itself is compromised in a number of pathological conditions (355, 363, 600, 853, 888, 1022).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [355]
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- Authors
- Ghosh, A., & Stuehr, D. J.
- Affiliations
- Cleveland Clinic (US)
- Venue
- Antioxidants & Redox Signaling
- Publisher
- SAGE Publications
- Published
- 2017-02
- Volume
- 26
- Issue
- 4
- Pages
- 182-190
- ISSN
- 1523-0864 (ISSN-L)
- 1557-7716
- PMC
- PMC5278824
- 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
- green
- www.ncbi.nlm.nih.gov
- 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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