Heme oxygenase-1: molecular mechanisms of gene expression in oxygen-related stress. Review uri icon

Overview

MeSH

  • Animals
  • Enzyme Activation
  • Glutathione
  • Heme Oxygenase-1
  • Humans
  • Hyperoxia
  • Hypoxia
  • Iron
  • Membrane Proteins
  • Oxidation-Reduction
  • Reactive Oxygen Species
  • Signal Transduction
  • Transcription, Genetic

MeSH Major

  • Gene Expression Regulation, Enzymologic
  • Heme Oxygenase (Decyclizing)
  • Oxidative Stress

abstract

  • Disturbances of intracellular redox equilibrium may alter eukaryotic gene expression patterns in the manifestation of an adaptive stress response. The inducible heme oxygenase-1 gene, ho-1, responds dramatically to changes in cellular redox potential provoked by multiple agents (oxidants, xenobiotics, reactive oxygen species, nitric oxide, and ultraviolet-A radiation) as well as deviations in oxygen tension in excess or deficit of normal physiological levels. This dual response to hyperoxic and hypoxic states renders ho-1 an intriguing model system for studying oxygen-regulated gene expression. The complexation or depletion of reduced glutathione apparently represents an underlying mechanism by which oxidants trigger the response. Chelatable iron levels also influence the induction of ho-1 as evidenced by the inhibitory effects of iron-chelating compounds. Redox-sensitive protein kinase cascades (e.g., mitogen-activated protein kinases) participate in ho-1 regulation. Recent progress in understanding ho-1 transcription has identified two distal enhancer regions (E1, E2) in the mouse ho-1 gene that mediate the response to many inducing conditions. This review will examine the potential roles of iron, glutathione, and reactive oxygen species in the upstream events leading to ho-1 activation following oxygen related stress.

publication date

  • August 2002

has subject area

  • Animals
  • Enzyme Activation
  • Gene Expression Regulation, Enzymologic
  • Glutathione
  • Heme Oxygenase (Decyclizing)
  • Heme Oxygenase-1
  • Humans
  • Hyperoxia
  • Hypoxia
  • Iron
  • Membrane Proteins
  • Oxidation-Reduction
  • Oxidative Stress
  • Reactive Oxygen Species
  • Signal Transduction
  • Transcription, Genetic

Research

keywords

  • Journal Article
  • Review

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1089/15230860260220120

PubMed ID

  • 12230874

Additional Document Info

start page

  • 625

end page

  • 632

volume

  • 4

number

  • 4