Nitric oxide blocks cellular heme insertion into a broad range of heme proteins
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Although the insertion of heme into proteins enables their function in bioenergetics, metabolism, and signaling, the mechanisms and regulation of this process are not fully understood. We developed a means to study cellular heme insertion into apo-protein targets over a 3-h period and then investigated how nitric oxide (NO) released from a chemical donor (NOC-18) might influence heme (protoporphyrin IX) insertion into seven targets that present a range of protein structures, heme ligation states, and functions (three NO synthases, two cytochrome P450's, catalase, and hemoglobin). NO blocked cellular heme insertion into all seven apo-protein targets. The inhibition occurred at relatively low (nM/min) fluxes of NO, was reversible, and did not involve changes in intracellular heme levels, activation of guanylate cyclase, or inhibition of mitochondrial ATP production. These aspects and the range of protein targets suggest that NO can act as a global inhibitor of heme insertion, possibly by inhibiting a common step in the process.
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Both COX-1 and COX-2 have been related to endothelial dysfunction.
“Two isoforms are expressed in mammals: COX-1 and COX-2, and both of them have been related to endothelial dysfunction (981, 982).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [982]
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Self-citation
- Authors
- Waheed, S. M., Ghosh, A., Chakravarti, R., Biswas, A., Haque, M. M., Panda, K., & Stuehr, D. J.
- Affiliations
- Cleveland Clinic (US)
- National Institute of Technology Rourkela (IN)
- University of Calcutta (IN)
- Corresponding author
- Stuehr, Dennis J.
- ORCID
- Venue
- Free Radical Biology and Medicine
- Publisher
- Elsevier BV
- Published
- 2010-06
- Volume
- 48
- Issue
- 11
- Pages
- 1548-1558
- ISSN
- 0891-5849 (ISSN-L)
- PMC
- PMC2866197
- OpenAlex
- W2012685167
- Cited by
- 62
- References
- 108
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 7 · 2023: 5 · 2022: 6 · 2021: 3 · 2020: 3 · 2019: 1 · 2018: 7 · 2017: 4 · 2016: 2 · 2015: 5 · 2014: 2 · 2013: 1 · 2012: 5
- FWCI
- 1.12
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Free Radical Biology and Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Heart, Lung, and Blood Institute (HL076491, P01HL076491)
- National Cancer Institute (CA-53914, R01CA053914)
- National Institute of General Medical Sciences (GM51491, R01GM051491)
- Topics
- 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
- Physical Sciences › Chemistry › Inorganic Chemistry › Metal-Catalyzed Oxygenation Mechanisms
- Keywords
- nitric oxide, heme insertion, protoporphyrin IX, heme proteins, apo protein, nitric oxide synthase, cytochrome P450, catalase, hemoglobin, NOC-18, reversible inhibition, heme ligation
- MeSH terms
- Animals, Catalase, Cell Line, Heme, Hemeproteins, Humans, Nitric Oxide, Nitroso Compounds, Protoporphyrins, Cytochrome P-450 CYP2D6, K562 Cells, Mice, Cytochrome P-450 CYP3A, Nitric Oxide Synthase Type II, Nitric Oxide Synthase Type I
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