Heme oxygenase expression in human central nervous system disorders.
In the normal mammalian CNS, heme oxygenase-2 (HO-2) is constitutively, abundantly, and fairly ubiquitously expressed, whereas heme oxygenase-1 (HO-1) mRNA and protein are confined to small populations of scattered neurons and neuroglia. Unlike ho-2, the ho-1 gene in neural (and many systemic) tissues is exquisitely sensitive to upregulation by a host of pro-oxidant and other noxious stimuli. In Alzheimer disease, HO-1 immunoreactivity is significantly augmented in neurons and astrocytes of the hippocampus and cerebral cortex relative to age-matched, nondemented controls and colocalizes to senile plaques, neurofibrillary tangles, and corpora amylacea. In Parkinson disease, HO-1 decorates Lewy bodies of affected dopaminergic neurons and is highly overexpressed in astrocytes residing within the substantia nigra. The ho-1 gene is also upregulated in glial cells within multiple sclerosis plaques; in the vicinity of human cerebral infarcts, hemorrhages, and contusions; and in various other degenerative and nondegenerative human CNS disorders. The products of the heme oxygenase reaction, free ferrous iron, carbon monoxide, and biliverdin/bilirubin, are all biologically active molecules that may profoundly influence tissue redox homeostasis under a wide range of pathophysiological conditions. Evidence adduced from whole animal and in vitro studies indicates that enhanced HO-1 activity may either ameliorate or exacerbate neural injury, effects likely contingent upon the specific model employed, the duration and intensity of HO-1 induction, and the chemistry of the local redox microenvironment. HO-1 hyperactivity also promotes mitochondrial sequestration of nontransferrin iron in oxidatively challenged astroglia and may thereby contribute to the pathological iron deposition and bioenergetic failure amply documented in aging and degenerating human neural tissues.
Schipper
Hyman M
HM
Lady Davis Institute for Medical Research, Sir Mortimer B. Davis Jewish General Hospital, 3755 Cote St. Catherine Road, Montreal QC H3T 1E2, Canada. hyman.schipper@mcgill.ca
D000375:Aging / Q000502:physiology; D000818:Animals; D001921:Brain / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D002493:Central Nervous System Diseases / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism*; D006801:Humans; D007501:Iron / Q000378:metabolism
D007501:Iron; D006419:Heme Oxygenase (Decyclizing)