Heme oxygenase-1: Redox regulation of a stress protein in lung and cell culture models

Stefan W. Ryter, Augustine M K Choi

Research output: Contribution to journalReview article

179 Scopus citations

Abstract

Reactive oxygen species (ROS) may contribute to tissue damage in many pathophysiological conditions and participate in physiological signaling processes. The mechanisms by which cells sense prooxidant states, and activate signaling pathways leading to adaptive responses, remain incompletely understood. Bacteria contain several transcriptional regulators (e.g., OxyR) and a low-molecular-weight heat shock protein (HSP33), whose activity increases upon oxidation of critical sulfhydryl residues. These proteins participate in cellular adaptation to oxidative stress. In higher organisms, heme oxygenase-1 (HO-1) has been widely studied as a model for redox-regulated gene expression. Expression of HO-1 responds to chemical and physical agents that directly or indirectly generate ROS. Depletion of cellular reduced glutathione may act as a signal for HO-1 transcriptional activation. Furthermore, antioxidants and metal-chelating compounds can modulate HO-1 expression. Several signaling molecules (e.g., mitogen-activated protein kinases), transcriptional regulators (activator protein-1, NF-E2-related factor-2, hypoxia-inducible factor-1, Bach-1), as well as two enhancer regions in the ho-1 5′ regulatory region, participate in the regulation of the ho-1 gene. HO-1 protein expression can occur in the lung in response to oxidative stress associated with infection, altered oxygen tension, and inflammatory diseases. HO-1 remains widely regarded as a protective mechanism against oxidative tissue injury.

Original languageEnglish (US)
Pages (from-to)80-91
Number of pages12
JournalAntioxidants and Redox Signaling
Volume7
Issue number1-2
DOIs
StatePublished - Jan 1 2005

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

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