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Heme Oxygenase‐1: Transducer of Pathological Brain Iron Sequestration under Oxidative Stress
Author(s) -
SCHIPPER HYMAN M.
Publication year - 2004
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1306.007
Subject(s) - oxidative stress , heme oxygenase , heme , proinflammatory cytokine , biliverdin , neuroinflammation , chemistry , reactive oxygen species , oxidative phosphorylation , biochemistry , biology , inflammation , immunology , enzyme
A bstract : Mechanisms responsible for the pathological deposition of redox‐active brain iron in human neurological disorders remain incompletely understood. Heme oxygenase‐1 (HO‐1) is a 32‐kDa stress protein that degrades heme to biliverdin, free iron, and carbon monoxide. In this chapter, we review evidence that (1) HO‐1 is overexpressed in CNS tissues affected by Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), and other degenerative and nondegenerative CNS diseases; (2) the pro‐oxidant effects of dopamine, hydrogen peroxide, b‐amyloid, and proinflammatory cytokines stimulate HO‐1 expression in some of these conditions; and (3) upregulation of HO‐1 in astrocytes exacerbates intracellular oxidative stress and promotes sequestration of nontransferrin‐derived iron by the mitochondrial compartment. A model is presented implicating glial HO‐1 induction as a “final common pathway” leading to pathological iron sequestration and mitochondrial insufficiency in a host of human CNS disorders.