Detection of nitrosyl complexes in human substantia nigra, in relation to Parkinson's disease.
Idiopathic Parkinson's disease (PD) involves a documentable decline in the activity of mitochondrial complex I in substantia nigra (1-3). We have EPR spectroscopy to investigate complex I in human substantia nigra and globus pallidus. EPR signals characteristic of the iron-sulfur centers of complexes I and II were observed with globus pallidus, with no significant difference between control and PD. These complex 1 signals could not be clearly observed in substantia nigra. Instead, nitric oxide (NO.) radicals in PD nigra were detected at g approximately 2.08, 1.98 due to [haem-NO] formation. Although an EPR signal indicative of haem-NO was observed with control nigra, it lacked the distinctive g approximately 1.98 trough observed with PD nigra. As PD is associated with a reactive gliosis, the difference in the haem-NO EPR signal, between control and PD nigra, may result from cytotoxic NO. generated by microglia in PD substantia nigra.
Shergill
J K
JK
Center for the Study of Metals in Biology and Medicine, King's College, University of London.
Cammack
R
R
Cooper
C E
CE
Cooper
J M
JM
Mann
V M
VM
Schapira
A H
AH
D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001344:Autopsy; D001923:Brain Chemistry; D004227:Dithionite; D004578:Electron Spin Resonance Spectroscopy; D005260:Female; D005917:Globus Pallidus / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D006454:Hemoglobins / Q000032:analysis*; D006801:Humans; D018482:Muscle, Skeletal / Q000737:chemistry; D009206:Myocardium / Q000737:chemistry; D009569:Nitric Oxide / Q000032:analysis*; D010300:Parkinson Disease / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D013378:Substantia Nigra / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology
D006454:Hemoglobins; C008657:nitrosyl hemoglobin; D004227:Dithionite; D009569:Nitric Oxide