Cited by 62Hemoglobin structure and functionHeme Oxygenase-1 and Carbon MonoxideMetal-Catalyzed Oxygenation Mechanisms

Nitric oxide blocks cellular heme insertion into a broad range of heme proteins

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Waheed, Syed Mohsin, Ghosh, Arnab, Chakravarti, Ritu, Biswas, Ashis, Haque, Mohammad Mahfuzul, Panda, Koustubh, Stuehr, Dennis J.·2010·Free Radical Biology and Medicine

Abstract

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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Crossref · 10.1016/j.freeradbiomed.2010.02.038

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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.
Venue
Free Radical Biology and Medicine
Publisher
Elsevier BV
Published
2010-06
Volume
48
Issue
11
Pages
1548-1558
ISSN
0891-5849 (ISSN-L)
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
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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