Overexpression of Neutrophil Neuronal Nitric Oxide Synthase in Parkinson's Disease

doi:10.1006/niox.2000.0288

Nitric Oxide

Volume 4, Issue 5, October 2000, Pages 534-539

https://doi.org/10.1006/niox.2000.0288 Get rights and content

Abstract

Much evidence supports a role of nitric oxide (·NO) and peroxynitrite (ONOO⁻) in experimental and idiopathic Parkinson's disease (PD); moreover, an overexpression of neuronal nitric oxide synthase (nNOS) was recently reported in the basal ganglia of PD patients. In accord, we previously found a 50% increased ·NO production rate during the respiratory burst of circulating neutrophils (PMN) from PD patients. As PMN express the nNOS isoform, the objective of the present study was to ascertain whether this increased ·NO production is representative of nNOS gene upregulation. PMN were isolated from blood samples obtained from seven PD patients and seven age- and sex-matched healthy donors; nNOS mRNA was amplified by reverse transcriptase–polymerase chain reaction and the products were hybridized with a probe for nNOS. Nitrotyrosine-containing proteins and nNOS were detected by Western blot and NO production rate was measured spectrophotometrically by the conversion of oxymyoglobin to metmyoglobin. The results showed that both ·NO production and protein tyrosine nitration were significantly increased in PMN isolated from PD patients (PD 0.09 ± 0.01 vs 0.06 ± 0.008 nmol min⁻¹ 10⁶ cells⁻¹; P < 0.05). In addition, five of the seven PD patients showed about 10-fold nNOS mRNA overexpression; while two of the seven PD patients showed an expression level similar to that of the controls; detection of nNOS protein was more evident in the former group. In summary, it is likely that overexpression of nNOS and formation of ONOO⁻ in PMN cells from PD patients emphasizes a potential causal role of ·NO in the physiopathology of the illness.

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Citation Excerpt :
The transgenic mice were more resistant to neurotoxicity induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) [179]. Furthermore, it has been revealed that polymorphonuclear cells isolated from PD patients are characterized by increased production rates of NO (∼30% increased rate), accumulation of the 3-nitrotyrosinated proteins and a neuronal upregulation of nNOS [180]. Also, an overexpression of nNOS protein was found in basal ganglia and circulating neutrophils of patients with PD.
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Brief CommunicationOverexpression of Neutrophil Neuronal Nitric Oxide Synthase in Parkinson's Disease

Abstract

Neurol. Clin.

Brain Res. Mol. Brain Res.

Nitric Oxide

FEBS Lett.

Methods Enzymol.

Anal. Biochem.

Free Rad. Biol. Med.

J. Biol. Chem.

J. Biol. Chem.

J. Neurol. Sci.

Neurochem. Int.

Brief Communication
Overexpression of Neutrophil Neuronal Nitric Oxide Synthase in Parkinson's Disease