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[Peroxynitrite production in cerebral ischemia]
S Takizawa1, H Hirabayashi, N Fukuyama
1Department of Neurology, Tokai University School of Medicine.
Rinsho Shinkeigaku = Clinical Neurology
|May 3, 2000
Summary
Peroxynitrite, a toxic molecule, was detected in ischemic brain using 3-nitro-L-tyrosine. Its production varies with reperfusion time and cell type, impacting therapeutic strategies for cerebral infarction.
Area of Science:
- Biochemistry
- Neuroscience
- Pathology
Context:
- Peroxynitrite (ONOO-) is a reactive nitrogen species formed from nitric oxide (NO) and superoxide.
- ONOO- causes cellular damage through oxidation and nitration, implicated in various pathologies.
- Its short half-life has historically prevented direct detection in the ischemic brain.
Purpose:
- To detect and characterize peroxynitrite formation in the ischemic brain.
- To investigate the temporal profile and cellular localization of peroxynitrite production.
- To elucidate the sources of nitric oxide involved in peroxynitrite generation during cerebral ischemia.
Summary:
- 3-nitro-L-tyrosine, a marker of peroxynitrite, was detected in the ischemic brain, with levels peaking 48 hours post-reperfusion.
- Nitrotyrosine levels were highest in the peri-infarct and core-infarct regions.
- Pharmacological studies suggest early peroxynitrite production from neuronal nitric oxide synthase (nNOS) and later production from inducible nitric oxide synthase (iNOS), predominantly in vascular cells.
Impact:
- Findings reveal peroxynitrite production is dynamic, dependent on the ischemic stage and NO-producing cell type.
- Identifies iNOS in vascular cells as a major contributor to nitrotyrosine formation.
- Provides crucial insights for optimizing therapeutic windows and selecting appropriate nitric oxide synthase inhibitors for cerebral infarction treatment.