Neural heme oxygenase-1 expression in idiopathic Parkinson's disease.
Heme oxygenase-1 is a cellular stress protein expressed in brain and other tissues in response to oxidative challenge and other noxious stimuli. In the present study, immunohistochemistry was used to assess HO-1 expression in various postmortem human brain specimens derived from PD and control subjects. In the substantia nigra of both PD and control specimens, moderate HO-1 immunoreactivity was consistently observed in neuromelanin-containing (dopaminergic) neurons. Lewy bodies in PD nigra neurons exhibited intense HO-1 immunostaining in their peripheries. In both PD and control specimens, neuronal HO-1 staining was faint or nondetectable in the other brain regions surveyed. The fraction of GFAP-positive astroglia expressing HO-1 in PD substantia nigra (77.1 +/- 12.3) was significantly greater than that observed in the substantia nigra of control subjects (18.7 +/- 7.1; P = 0.0015). In the other regions examined, percentages of GFAP-positive astroglia coexpressing HO-1 were relatively low and did not differ significantly (P > 0.05) between control and PD specimens. Upregulation of HO-1 in the substantia nigra of PD subjects supports the view that the affected tissue is experiencing chronic oxidative stress. In addition, excessive cellular levels of heme-derived free iron and carbon monoxide resulting from HO-1 overactivity may contribute to the pathogenesis of PD.
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Bloomfield Centre for Research in Aging, Lady Davis Institute for Medical Research, Sir Mortimer B. Davis-Jewish General Hospital, Montreal, Quebec, Canada.
Liberman
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Stopa
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D000368:Aged; D000369:Aged, 80 and over; D001253:Astrocytes / Q000201:enzymology; D015415:Biomarkers; D002248:Carbon Monoxide / Q000378:metabolism; D004298:Dopamine / Q000032:analysis; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism*; D051547:Heme Oxygenase-1; D006801:Humans; D016631:Lewy Bodies / Q000201:enzymology; D008543:Melanins / Q000032:analysis; D008565:Membrane Proteins; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000201:enzymology / Q000473:pathology; D009928:Organ Specificity; D018384:Oxidative Stress; D010300:Parkinson Disease / Q000201:enzymology*; D013378:Substantia Nigra / Q000201:enzymology
D015415:Biomarkers; D005904:Glial Fibrillary Acidic Protein; D008543:Melanins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C014121:neuromelanin; D002248:Carbon Monoxide; C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; D004298:Dopamine