The DOI matches its Crossref record; 240 of the 240 references it cites were found in a registry or an index.
Mechanisms of Cell Protection by Heme Oxygenase-1
Abstract
Heme oxygenases (HO) catabolize free heme, that is, iron (Fe) protoporphyrin (IX), into equimolar amounts of Fe 2+ , carbon monoxide (CO), and biliverdin. The stress-responsive HO-1 isoenzyme affords protection against programmed cell death. The mechanism underlying this cytoprotective effect relies on the ability of HO-1 to catabolize free heme and prevent it from sensitizing cells to undergo programmed cell death. This cytoprotective effect inhibits the pathogenesis of a variety of immune-mediated inflammatory diseases.
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In the citing paper
“Thus, HO-1 exerts cytoprotective effects by reducing the pro-oxidative activity of heme and by re-programming metabolic traits, thereby limiting tissue damage in the course of inflammatory processes, including sepsis (Gozzelino et al., 2010; Weis et al., 2017).”
From The Role of Iron Regulation in Immunometabolism and Immune-Related Disease (2019) · cites this paper as Gozzelino et al., 2010
In the citing paper
“Presumably, this occurs via a mechanism driven via the Fenton reaction in which hydrogen peroxide (H 2 O 2 ) oxidizes Fe 2+ , either within the context of the tetrapyrrole ring or when Fe is released from heme, to produce highly reactive hydroxyl radicals (OH .) [38,212].”
From The Iron age of host–microbe interactions (2015) · cites this paper as [38]
In the citing paper
“Briefly, labile heme sensitizes parenchyma cells to undergo programmed cell death in response to proinflammatory cytokines such as TNF [106] as well as other agonists such as Fas as well as ROS and RNS [38,190].”
From The Iron age of host–microbe interactions (2015) · cites this paper as [38]
In the citing paper
“Once released from hemoglobin, the redox activity of labile heme becomes pro-oxidant and cytotoxic [38,106,107,190] (Fig 4).”
From The Iron age of host–microbe interactions (2015) · cites this paper as [38]
In the citing paper
“The pathogenic effects exerted by extracellular hemoglobin and labile heme are countered by adaptive responses that converge at the level of heme catabolism by HO-1 [38,219], providing tissue damage control and disease tolerance to systemic infections [103,105,106] (Fig 4).”
From The Iron age of host–microbe interactions (2015) · cites this paper as [38]
In the citing paper
“When coupled to other mechanisms regulating Fe homeostasis, HO-1 avoids tissue Fe overload and tissue damage while sustaining Fe supply to erythropoiesis to maintain Fe homeostasis during infection [38,54,219,220] (Fig 4).”
From The Iron age of host–microbe interactions (2015) · cites this paper as [38]
In the citing paper
“The most abundant pool of Fe in mammals are the prosthetic heme groups of hemoglobin in red blood cells (RBC), followed by the heme groups of myoglobin in muscle cells and those of cytochromes and other ubiquitously expressed hemoproteins in all cells[38,54].”
From The Iron age of host–microbe interactions (2015) · cites this paper as [38]
In the citing paper
“Moreover, recent studies demonstrate the mechanisms leading to the unfavorable effects of free hemoglobin including oxidation and production of ferryl hemoglobin and heme generation [36-38].”
From Free hemoglobin concentration in severe sepsis: methods of measurement and prediction of outcome (2012) · cites this paper as [38]
In the citing paper
“In addition, the reduced abundance of CO and bilirubin, two end-products of the HO-1 pathway, further contributes to increased or prolonged oxidative stress, as these molecules have radical scavenging capacities and anti-inflammatory activities (Gozzelino et al., 2010).”
From Heme oxygenase 1 controls early innate immune response of macrophages to Salmonella Typhimurium infection: Heme oxygenase 1 expression affects Salmonella infection (2016) · cites this paper as Gozzelino et al., 2010
In the citing paper
“Up-regulation of HO-1 during malaria or sepsis was demonstrated in association with infection tolerance and limitation of tissue damage resulting in an improved survival (Gozzelino et al., 2010; Larsen et al., 2010).”
From Heme oxygenase 1 controls early innate immune response of macrophages to Salmonella Typhimurium infection: Heme oxygenase 1 expression affects Salmonella infection (2016) · cites this paper as Gozzelino et al., 2010
Citations
Cites
1 retracted
Items 201–240 of 240
Hemin induces neuroglobin expression in neural cells
Zhu, Y., Sun, Y., Jin, K., & Greenberg, D. A. (2002) · Blood · doi:10.1182/blood-2002-01-0280 · Cited by 90
Bainbridge, S. A., & Smith, G. N. (2005) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2004.11.002 · Cited by 82
Denschlag, D. (2004) · Molecular Human Reproduction · doi:10.1093/molehr/gah024 · Cited by 81
Receptor-mediated transport of heme by hemopexin regulates gene expression in mammalian cells
Alam, J., & Smith, A. (1989) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)84616-1 · Cited by 80
Soares, M. P., Muniappan, A., Kaczmarek, E., Koziak, K., Wrighton, C. J., Steinhäuslin, F., Ferran, C. J., Winkler, H. J. S., Bach, F. H., & Anrather, J. (1998) · The Journal of Immunology · doi:10.4049/jimmunol.161.9.4572 · Cited by 80
Self-citationRole of iron and ferritin in TNFα‐induced apoptosis in HeLa cells
Cozzi, A., Levi, S., Corsi, B., Santambrogio, P., Campanella, A., Gerardi, G., & Arosio, P. (2003) · FEBS Letters · doi:10.1016/s0014-5793(03)00114-5 · Cited by 76
Protection From Ischemic Heart Injury by a Vigilant Heme Oxygenase-1 Plasmid System
Tang, Y., Tang, Y., Zhang, Y. C., Qian, K., Shen, L., & Phillips, M. I. (2004) · Hypertension · doi:10.1161/01.hyp.0000120152.27263.87 · Cited by 73
Intravascular haemolysis and acute renal failure following potassium dichromate poisoning
Sharma, B. K., Singhal, P. C., & Chugh, K. S. (1978) · Postgraduate Medical Journal · doi:10.1136/pgmj.54.632.414 · Cited by 72
Bilirubin Can Induce Tolerance to Islet Allografts
Wang, H., Lee, S. S., Dell’Agnello, C., Tchipashvili, V., D’Avilla, J., Czismadia, E., Chin, B. Y., & Bach, F. H. (2005) · Endocrinology · doi:10.1210/en.2005-0632 · Cited by 72
Gertz, M. A. (2006) · Hematology · doi:10.1182/asheducation-2006.1.19 · Cited by 72
High-Mobility Group Box 1 Contributes to Lethality of Endotoxemia in Heme Oxygenase-1–Deficient Mice
Takamiya, R., Hung, C.-C., Hall, S. R. R., Fukunaga, K., Nagaishi, T., Maeno, T., Owen, C. A., Macias, A. A., Fredenburgh, L. E., Ishizaka, A., et al. (2008) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2008-0331oc · Cited by 69
Effect of hemin on site-specific phosphorylation of eukaryotic initiation factor 2.
Tahara, S. M., Traugh, J. A., Sharp, S. B., Lundak, T. S., Safer, B., & Merrick, W. C. (1978) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.75.2.789 · Cited by 69
Immenschuh, S., Iwahara, S.-I., Satoh, H., Nell, C., Katz, N. R., & Müller‐Eberhard, U. (1995) · Biochemistry · doi:10.1021/bi00041a018 · Cited by 68
Immunology of pregnancy: cellular mechanisms allowing fetal survival within the maternal uterus
Zenclussen, A. C., Schumacher, A., Zenclussen, M. L., Wafula, P. O., & Volk, H. (2007) · Expert Reviews in Molecular Medicine · doi:10.1017/s1462399407000294 · Cited by 62
Heme oxygenase and iron: from bacteria to humans
Li, C., & Stocker, R. (2009) · Redox Report · doi:10.1179/135100009x392584 · Cited by 60
Adenine Nucleotide Translocator Transports Haem Precursors into Mitochondria
Azuma, M., Kabe, Y., Kuramori, C., Kondo, M., Yamaguchi, Y., & Handa, H. (2008) · PLoS ONE · doi:10.1371/journal.pone.0003070 · Cited by 54
Prosthesis-induced hemolysis: mechanisms and quantification of shear stress.
Ellis, J. T., Wick, T. M., & Yoganathan, A. P. (1998) · PubMed · Cited by 53
Heme oxygenase-1 is not required for mouse regulatory T cell development and function
Zelenay, S., Chora, Â. F., Soares, M. P., & Demengeot, J. (2006) · International Immunology · doi:10.1093/intimm/dxl116 · Cited by 52
Self-citationXie, C., Zhang, N., Zhou, H., Li, J., Li, Q., Zarubin, T., Lin, S., & Han, J. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.15.6673-6681.2005 · Cited by 52
The Intestinal Heme Transporter Revealed
Rouault, T. A. (2005) · Cell · doi:10.1016/j.cell.2005.08.027 · Cited by 47
Dengue Virus‐Associated Hemophagocytic Syndrome and Dyserythropoiesis: A Case Report
Lu, P., Hsiao, H.-H., Tsai, J., Chen, T., Chen, T., Lin, S., & Feng, M. (2005) · The Kaohsiung Journal of Medical Sciences · doi:10.1016/s1607-551x(09)70274-8 · Cited by 46
Heme binding to albuminoid proteins is the result of recent evolution
Fasano, M., Fanali, G., Leboffe, L., & Ascenzi, P. (2007) · IUBMB Life · doi:10.1080/15216540701474523 · Cited by 43
Damage control in host–pathogen interactions
Medzhitov, R. M. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0908451106 · Cited by 42
Hyperoxic Regulation of Lung Heme Oxygenase in Neonatal Rats
Dennery, P. A., Rodgers, P. A., Lum, M. A., Jennings, B. C., & Shokoohi, V. (1996) · Pediatric Research · doi:10.1203/00006450-199612000-00007 · Cited by 38
Therapeutic Applications of Human Heme Oxygenase Gene Transfer and Gene Therapy
Abraham, N. G. (2003) · Current Pharmaceutical Design · doi:10.2174/1381612033453758 · Cited by 36
Myoglobin expression in L6 muscle cells. Role of differentiation and heme.
Graber, S. G., & Woodworth, R. C. (1986) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)67631-8 · Cited by 35
Immune hemolysis-serological and clinical aspects
Prüß, A., Salama, A., Ahrens, N., Hansen, A., Kiesewetter, H., Koscielny, J., & D�rner, T. (2003) · Clinical and Experimental Medicine · doi:10.1007/s10238-003-0009-4 · Cited by 34
Intravascular Hemolysis in Aortic Stenosis
Tsuji, A., Tanabe, M., Onishi, K., Kitamura, T., 沖中, 務., Ito, M., Isaka, N., & Nakano, T. (2004) · Internal Medicine · doi:10.2169/internalmedicine.43.935 · Cited by 30
Daly, J. J., Haeusler, M., Hogan, C., & Wood, E. M. (2006) · British Journal of Haematology · doi:10.1111/j.1365-2141.2006.06177.x · Cited by 29
Binding of Hæmatin by Human Serum Albumin
Little, H. N., & Neilands, J. B. (1960) · Nature · doi:10.1038/188913a0 · Cited by 29
Extracellular acidosis induces heme oxygenase-1 expression in vascular smooth muscle cells
Christou, H. A., Bailey, N. A., Kluger, M. S., Mitsialis, S. A., & Kourembanas, S. (2005) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00937.2004 · Cited by 28
A key role for heme oxygenase-1 in nitric oxide resistance in murine motor neurons and glia
Bishop, A., Yet, S., Lee, M.-E., Perrella, M. A., & Demple, B. (2004) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2004.10.010 · Cited by 26
Immenschuh, S., Nell, C., Iwahara, S.-I., Katz, N. R., & Müller‐Eberhard, U. (1997) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1997.6166 · Cited by 20
Reactions of Superoxide with Hemoglobin
Winterbourn, C. C. (2018) · doi:10.1201/9781351072922-29 · Cited by 17
Reiter, T. A., Pang, B., Dedon, P. C., & Demple, B. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m602634200 · Cited by 16
VEGF: is it just an inducer of heme oxygenase-1 expression?
Soares, M. P. (2004) · Blood · doi:10.1182/blood-2003-11-3879 · Cited by 15
Self-citationHemolysis following thermal injury and depression of reticuloendothelial system phagocytic function.
Dj, L. (1981) · PubMed · Cited by 13
Grosser, N., & Schr�der, H. (2004) · Herz · doi:10.1007/s00059-004-2530-3 · Cited by 11
Carrell, R. W., & Winterbourn, C. C. (1982) · PubMed · Cited by 10
Karai, I., Fukumoto, K., & Horiguchi, S. (1982) · International Archives of Occupational and Environmental Health · doi:10.1007/bf00432490 · Cited by 9
Research works printed but not linked: 5
- Otterbein LE, 1999, Am. J. Physiol. Renal Physiol., 276, L688
- Wang H, 2005, Endocrinology, 147, 262
- Loegering DJ, 1981, J. Traumatol., 21, 130
- Carrell RW, 1980, Tex. Rep. Biol. Med., 40, 431
- Ellis JT, 1998, J. Heart Valve Dis., 7, 376
Cited by
Sorted by citations
Modulation of oxidative stress as an anticancer strategy
Gorrini, C., Harris, I. S., & Mak, T. W. (2013) · Nature Reviews Drug Discovery · doi:10.1038/nrd4002 · Cited by 3,579
Hayes, J. D., Dinkova-Kostova, A. T., & Tew, K. D. (2020) · Cancer Cell · doi:10.1016/j.ccell.2020.06.001 · Cited by 2,654
Łoboda, A., Damulewicz, M., Pyza, E., Józkowicz, A., & Dulak, J. (2016) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-016-2223-0 · Cited by 2,709
Transcriptional Regulation by Nrf2
Tonelli, C., Chio, I. I. C., & Tuveson, D. A. (2017) · Antioxidants and Redox Signaling · doi:10.1089/ars.2017.7342 · Cited by 2,280
Disease Tolerance as a Defense Strategy
Medzhitov, R., Schneider, D. S., & Soares, M. P. (2012) · Science · doi:10.1126/science.1214935 · Cited by 1,718
Self-citation
Metadata
- Authors
- Gozzelino, R., Jeney, V., & Soares, M. P.
- Affiliations
- Instituto Gulbenkian de Ciência (PT)
- Instituto Gulbenkian de Ciência, Oeiras, Portugal;
- Venue
- Annual Review of Pharmacology and Toxicology
- Publisher
- Annual Reviews
- Published
- 2010-02-01
- Volume
- 50
- Issue
- 1
- Pages
- 323-354
- ISSN
- 0362-1642 (ISSN-L)
- 1545-4304
- OpenAlex
- W2162853795
- Cited by
- 1,241
- References
- 237
- Citations by year
- 2026: 66 · 2025: 61 · 2024: 55 · 2023: 72 · 2022: 92 · 2021: 114 · 2020: 101 · 2019: 60 · 2018: 87 · 2017: 75 · 2016: 65 · 2015: 99 · 2014: 77 · 2013: 69 · 2012: 74
- FWCI
- 6.01
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Annual Review of Pharmacology and Toxicology (publishedVersion)
- PubMed (publishedVersion)
- University of Debrecen Electronic Archive (University of Debrecen) (submittedVersion)
- 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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Porphyrin Metabolism and Disorders
- Keywords
- heme oxygenase-1, heme degradation, carbon monoxide, biliverdin, bilirubin, programmed cell death, cytoprotection, immune-mediated inflammatory diseases, stress response
- MeSH terms
- Animals, Biliverdine, Carbon Monoxide, Heme, Humans, Inflammation, Tumor Necrosis Factor-alpha, Gene Expression Regulation, Enzymologic, Apoptosis, Cytoprotection, Heme Oxygenase-1
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