Cited by 499Heme Oxygenase-1 and Carbon MonoxideHemoglobin structure and functionNitric Oxide and Endothelin Effects

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Heme oxygenase/carbon monoxide signaling pathways: Regulation and functional significance

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Ryter, Stefan W., Otterbein, Leo E., Morse, Danielle, Choi, Augustine M.K.·2002·Molecular and Cellular Biochemistry

DOI 10.1023/a:1015957026924PMC PMC7101540

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Abstract

Carbon monoxide (CO), a gaseous second messenger, arises in biological systems during the oxidative catabolism of heme by the heme oxygenase (HO) enzymes. HO exists as constitutive (HO-2, HO-3) and inducible isoforms (HO-1), the latter which responds to regulation by multiple stress-stimuli. HO-1 confers protection in vitro and in vivo against oxidative cellular stress. Although the redox active compounds that are generated from HO activity (i.e. iron, biliverdin-IXalpha, and bilirubin-IXa) potentially modulate oxidative stress resistance, increasing evidence points to cytoprotective roles for CO. Though not reactive, CO regulates vascular processes such as vessel tone, smooth muscle proliferation, and platelet aggregation, and possibly functions as a neurotransmitter. The latter effects of CO depend on the activation of guanylate cyclase activity by direct binding to the heme moiety of the enzyme, stimulating the production of cyclic 3':5'-guanosine monophosphate. CO potentially interacts with other intracellular hemoprotein targets, though little is known about the functional significance of such interactions. Recent progress indicates that CO exerts novel anti-inflammatory and anti-apoptotic effects dependent on the modulation of the p38 mitogen activated protein kinase (MAPK)-signaling pathway. By virtue of these effects, CO confers protection in oxidative lung injury models, and likely plays a role in HO-1 mediated tissue protection.

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Authors: Ryter, S. W., Otterbein, L. E., Morse, D., & Choi, A. M. K.
Affiliations: University of Pittsburgh Medical Center (US)
Corresponding author: Ryter, Stefan W.
ORCID: Ryter, Stefan W.
Otterbein, Leo E.
Choi, Augustine M.K.
Venue: Molecular and Cellular Biochemistry
Publisher: Springer Science and Business Media LLC
Published: 2002-05
Volume: 234-235
Issue: 1
Pages: 249-263
ISSN: 0300-8177 (ISSN-L)
1573-4919
DOI: 10.1023/a:1015957026924
PMC: PMC7101540
OpenAlex: W2171750543
Cited by: 497
References: 209
Citations by year: 2026: 5 · 2025: 4 · 2024: 7 · 2023: 13 · 2022: 12 · 2021: 12 · 2020: 21 · 2019: 6 · 2018: 14 · 2017: 25 · 2016: 19 · 2015: 19 · 2014: 29 · 2013: 28 · 2012: 26
FWCI: 8.34
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.springernature.com/gp/researchers/text-and-data-mining (tdm)
www.springernature.com/gp/researchers/text-and-data-mining (vor)
Locations: Molecular and Cellular Biochemistry (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heme Oxygenase-1 and Carbon Monoxide
Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Hemoglobin structure and function
Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
Keywords: carbon monoxide, heme oxygenase, heme oxygenase-1, heme oxygenase-2, oxidative stress, biliverdin, bilirubin, guanylate cyclase, cyclic GMP, cytoprotection, anti-inflammatory activity, anti-apoptotic effects, p38 MAPK signaling, oxidative lung injury, vascular tone, platelet aggregation, neurotransmitters
MeSH terms: Animals, Anti-Inflammatory Agents, Carbon Monoxide, Heme Oxygenase (Decyclizing), Humans, Inflammation, Isoenzymes, Stress, Physiological, Signal Transduction, Gene Expression Regulation, Enzymologic, Oxidative Stress

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Heme oxygenase/carbon monoxide signaling pathways: Regulation and functional significance

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