Heme Oxygenase-1 Deficiency and Oxidative Stress: A Review of 9 Independent Human Cases and Animal Models

Int J Mol Sci. 2021 Feb 3;22(4):1514. doi: 10.3390/ijms22041514.

Abstract

Since Yachie et al. reported the first description of human heme oxygenase (HO)-1 deficiency more than 20 years ago, few additional human cases have been reported in the literature. A detailed analysis of the first human case of HO-1 deficiency revealed that HO-1 is involved in the protection of multiple tissues and organs from oxidative stress and excessive inflammatory reactions, through the release of multiple molecules with anti-oxidative stress and anti-inflammatory functions. HO-1 production is induced in vivo within selected cell types, including renal tubular epithelium, hepatic Kupffer cells, vascular endothelium, and monocytes/macrophages, suggesting that HO-1 plays critical roles in these cells. In vivo and in vitro studies have indicated that impaired HO-1 production results in progressive monocyte dysfunction, unregulated macrophage activation and endothelial cell dysfunction, leading to catastrophic systemic inflammatory response syndrome. Data from reported human cases of HO-1 deficiency and numerous studies using animal models suggest that HO-1 plays critical roles in various clinical settings involving excessive oxidative stress and inflammation. In this regard, therapy to induce HO-1 production by pharmacological intervention represents a promising novel strategy to control inflammatory diseases.

Keywords: HO-1 deficiency; heme oxygenase; inflammation; oxidative stress.

Publication types

  • Review

MeSH terms

  • Anemia, Hemolytic / metabolism*
  • Animals
  • Growth Disorders / metabolism*
  • Heme Oxygenase-1 / deficiency*
  • Heme Oxygenase-1 / metabolism*
  • Humans
  • Inflammation
  • Iron Metabolism Disorders / metabolism*
  • Oxidative Stress*

Substances

  • Heme Oxygenase-1

Supplementary concepts

  • Heme Oxygenase 1 Deficiency

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