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Hemoglobin provides protection against lethal endotoxemia in rats: the role of heme oxygenase-1.
Abstract
Heme oxygenase (HO) catalyzes the rate-limiting step in the degradation of heme to bilirubin. HO-1 is highly induced by heme, its major substrate, and nonheme products, including metal ions and hormones. Interest in HO-1 has been stimulated recently by observations that HO-1 is also highly induced in response to oxidative stress in vitro. The physiologic significance of HO-1 induction following oxidant injury in vivo, however, is poorly understood. In a rat model of lipopolysaccharide endotoxin (LPS)-induced lung injury and sepsis, we demonstrate that the lung responds to LPS by expressing high levels of HO-1 mRNA and enzyme activity. We hypothesize that this HO-1 induction could play a critical role in the lung's defense against LPS. Pretreatment of rats with hemoglobin, a potent inducer of HO-1, resulted in HO-1 induction and more importantly provided complete protection against subsequent lethal endotoxemia (100% survival). Tin protoporphyrin, a competitive inhibitor of HO, blocked this protective effect of hemoglobin and rendered the rats more susceptible to a lethal dose of LPS. Taken together, these data strongly implicate HO-1 in playing an important role in the defense against endotoxic shock, with potential therapeutic implications.
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Cited by
Carbon monoxide has anti-inflammatory effects involving the mitogen-activated protein kinase pathway
Otterbein, L. E., Bach, F. H., Alam, J., Soares, M., Tao Lu, H., Wysk, M., Davis, R. J., Flavell, R. A., & Choi, A. M. K. (2000) · Nature Medicine · doi:10.1038/74680 · Cited by 2,153
Self-citationHeme oxygenase-1 mediates the anti-inflammatory effect of interleukin-10 in mice
Lee, T.-S., & Chau, L.-Y. (2002) · Nature Medicine · doi:10.1038/nm0302-240 · Cited by 1,019
Carbon Monoxide Generated by Heme Oxygenase 1 Suppresses Endothelial Cell Apoptosis
Brouard, S., Otterbein, L. E., Anrather, J., Tobiasch, E., Bach, F. H., Choi, A. M. K., & Soares, M. P. (2000) · The Journal of Experimental Medicine · doi:10.1084/jem.192.7.1015 · Cited by 984
Self-citationHeme oxygenase: colors of defense against cellular stress
Otterbein, L. E., & Choi, A. M. K. (2000) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.2000.279.6.l1029 · Cited by 870
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Metadata
- Authors
- Otterbein, L., Sylvester, S. L., & Choi, A. M.
- Venue
- American Journal of Respiratory Cell and Molecular Biology
- Publisher
- Oxford University Press (OUP)
- Published
- 1995-11
- Volume
- 13
- Issue
- 5
- Pages
- 595-601
- ISSN
- 1044-1549 (ISSN-L)
- 1535-4989
- OpenAlex
- W2124595022
- Cited by
- 306
- References
- 0
- FWCI
- 3.20
- Type
- journal article
- Language
- en
- Open access
- closed
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- CoChat. (2026). Citation check: Hemoglobin provides protection against lethal endotoxemia in rats: the role of heme oxygenase-1. https://app.cochat.ai/papers/10.1165/ajrcmb.13.5.7576696
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- Otterbein, L., Sylvester, S. L., & Choi, A. M. (1995). Hemoglobin provides protection against lethal endotoxemia in rats: the role of heme oxygenase-1. American Journal of Respiratory Cell and Molecular Biology. https://doi.org/10.1165/ajrcmb.13.5.7576696
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
