Location of Repository

Integrative Survival Response Evoked by Heme Oxygenase-1 and Heme Metabolites

By Hyun-Ock Pae, Eun-Cheol Kim and Hun-Taeg Chung


Heme oxygenase (HO) catalyzes the rate-limiting step in heme degradation to produce carbon monoxide (CO), iron, and biliverdin. Biliverdin is subsequently converted to bilirubin by its reductase, and iron is recycled for heme synthesis. The inducible HO isoform, HO-1, is involved in the protection of multiple tissues and organs. The mechanism of protective actions of HO-1 has not been completely elucidated, but recent evidence suggests that one or more of heme metabolites can mediate the protective effects of HO-1. Particularly, CO mimics the antioxidant, anti-inflammatory, anti-apoptotic and antiproliferative actions of HO-1. Many of these effects of CO depend on the production of cyclic guanosine monophosphate (cGMP), and the modulation of mitogen-activated protein kinase (MAPK) pathways. The transcription factors, including nuclear factor E2-related factor-2 (Nrf2), and their upstream kinases, including MAPK pathway, play an important regulatory role in HO-1 expression by dietary antioxidants and drugs. This review attempts to concisely summarize the molecular and biochemical characteristics of HO-1, with a discussion on the mechanisms of signal transduction and gene regulation that mediate the induction of HO-1 by dietary antioxidants and drugs. In addition, the cytoprotective roles of HO-1 shall be discussed from the perspective of each of the metabolic by-products

Topics: Serial Review
Publisher: the Society for Free Radical Research Japan
OAI identifier: oai:pubmedcentral.nih.gov:2386522
Provided by: PubMed Central
Download PDF:
Sorry, we are unable to provide the full text but you may find it at the following location(s):
  • http://www.pubmedcentral.nih.g... (external link)
  • Suggested articles



    1. (2005). Alpha-lipoic acid-induced heme oxygenase-1 expression is mediated by nuclear factor erythroid 2-related factor 2 and p38 mitogen-activated protein kinase in human monocytic cells.
    2. (2002). Caffeic acid phenethyl ester and curcumin: a novel class of heme oxygenase-1 inducers.
    3. (2007). Carbon monoxide and bilirubin: potential therapies for pulmonary/vascular injury and disease.
    4. (1997). Carbon monoxide controls the proliferation of hypoxic vascular smooth muscle cells.
    5. (2007). Carbon monoxide induces heme oxygenase-1 via activation of protein kinase R-like endoplasmic reticulum kinase and inhibits endothelial cell apoptosis triggered by endoplasmic reticulum stress.
    6. (2002). Carbon monoxide inhibits human airway smooth muscle cell proliferation via mitogen-activated protein kinase pathway.
    7. (2006). Carbon monoxide mediates heme oxygenase 1 induction via Nrf2 activation in hepatoma cells.
    8. (2004). Carbon monoxide produced by heme oxygenase-1 suppresses T cell proliferation via inhibition of IL-2 production.
    9. (2002). Carbon monoxide protects pancreatic beta-cells from apoptosis and improves islet function/survival after transplantationDiabetes,
    10. (2005). Carbon monoxide-releasing molecules (CO-RMs) attenuate the inflammatory response elicited by lipopolysaccharide in RAW264.7 murine macrophages.
    11. (2006). Carbon monoxide: the bad and the good side of the coin, from neuronal death to anti-inflammatory activity.
    12. (2006). Comparative effects of curcuminoids on endothelial heme oxygenase-1 expression: ortho-methoxy groups are essential to enhance heme oxygenase activity and protection.
    13. (2003). Curcumin activates the haem oxygenase-1 gene via regulation of Nrf2 and the antioxidant-responsive element.
    14. (2007). Curcumin induces heme oxygenase 1 through generation of reactive oxygen species, p38 activation and phosphatase inhibition.
    15. (2006). Drastic effect of several caffeic acid derivatives on the induction of heme oxygenase-1 expression revealed by quantitative real-time RT-PCR.
    16. (2007). Emerging role of Nrf2 in protecting against hepatic and gastrointestinal disease.
    17. (2004). Haem oxygenase-1: a target for dietary antioxidants.
    18. (2007). Heme as a magnificent molecule with multiple missions: heme determines its own fate and governs cellular homeostasis.
    19. (1997). Heme oxygenase 1 is required for mammalian iron reutilization.
    20. (2005). Heme oxygenase and heme degradation.
    21. (2006). Heme oxygenase-1 as a potential therapeutic target for hepatoprotection.
    22. (2002). Heme oxygenase-1 deficiency: The first autopsy case.
    23. (2004). Heme oxygenase-1 modulates early inflammatory responses: evidence from the heme oxygenase-1-deficient mouse.
    24. (2004). Heme oxygenase-1: a new therapeutic target for inflammatory bowel disease.
    25. (2005). Heme oxygenase-1: from bench to bedside.
    26. (2006). Heme oxygenase-1/ carbon monoxide: from basic science to therapeutic applications.
    27. (2005). Heme, heme oxygenase and ferritin in vascular endothelial cell injury.
    28. (2007). Heme, heme oxygenase, and ferritin: how the vascular endothelium survives (and dies) in an iron-rich environment.
    29. (2007). How many transcription factors does it take to turn on the heme oxygenase-1 gene?.
    30. (2007). Human heme oxygenase-1 deficiency: a lesson on serendipity in the discovery of the novel disease.
    31. (2005). Induction of heme oxygenase 1 by moderately oxidized low-density lipoproteins in human vascular smooth muscle cells: role of mitogen-activated protein kinases and Nrf2. Free Radic.
    32. (2004). Induction of heme oxygenase-1 is involved in anti-proliferative effects of paclitaxel on rat vascular smooth muscle cells.
    33. (2008). Inhibition of platelet aggregationSurvival Response by HO-1 and Its Products
    34. (2006). Involvement of Nrf2, p38, B-Raf, and nuclear factor-kappaB, but not phosphatidylinositol 3-kinase, in induction of hemeoxygenase-1 by dietary polyphenols.
    35. (2002). Molecular and cellular mechanisms of iron homeostasis and toxicity in mammalian cells.
    36. (2003). Nitric oxide-mediated cytoprotection of hepatocytes from glucose deprivation-induced cytotoxicity: involvement of heme oxygenase-1.
    37. (2007). Nrf2 gene transfer induces antioxidant enzymes and suppresses smooth muscle cell growth in vitro and reduces oxidative stress in rabbit aorta in vivo.
    38. (2006). Nrf2-deficient mice have an increased susceptibility to dextran sulfate sodium-induced colitis.
    39. (1999). Oxidative stress causes enhanced endothelial cell injury in human heme oxygenase-1 deficiency.
    40. (1997). Reduced stress defense in heme oxygenase 1-deficient cells.
    41. (2007). Roles of heme oxygenase-1 in curcumin-induced growth inhibition in rat smooth muscle cells.
    42. (2007). Therapeutic applications of bilirubin and biliverdin in transplantation.
    43. (2000). Tubular injury as a cardinal pathologic feature in human heme oxygenase-1 deficiency.

    To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.