Effect of phosphorylated c-Jun expression on COX-2 expression in the substantia nigra of MPTP mouse model of subacute Parkinson disease.
- Author:
Yong-Sheng WANG
1
,
2
;
Jian-Ping ZHOU
;
Zi-Feng WEI
;
Qing-You TIAN
;
Hong-Xia ZHOU
;
Yu-Xin ZHANG
Author Information
- Publication Type:Journal Article
- MeSH: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; pharmacology; Animals; Anthracenes; pharmacology; Blotting, Western; Cell Death; drug effects; Cyclooxygenase 2; metabolism; Disease Models, Animal; Dopamine; metabolism; Gene Expression Regulation, Enzymologic; drug effects; Humans; Immunohistochemistry; MAP Kinase Signaling System; drug effects; Male; Mice; Mice, Inbred C57BL; Neurons; pathology; Parkinson Disease; enzymology; etiology; metabolism; pathology; Phosphoproteins; metabolism; Phosphorylation; Proto-Oncogene Proteins c-jun; metabolism; Substantia Nigra; drug effects; metabolism
- From: Journal of Southern Medical University 2007;27(8):1199-1205
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo investigate the effect of phophorylated c-Jun (p-c-Jun) expression on the expression of COX-2 in the substantia nigra (SN) of the MPTP mouse model of subacute Parkinson disease (PD) and explore the possible mechanism of the dopaminergic (DA) neuron death in PD.
METHODSC57BL/6N mice were treated with MPTP to establish subacute PD model. The changes of TH-, COX-2- and p-c-Jun-positive cells, and the expression levels of TH, COX-2 and p-c-Jun in the SN in the midbrain were observed with inmmunohistochemistry and Western blotting before and after administration of SP600125, a specific JNK inhibitor.
RESULTSCompared with the mice in control group, the PD mice exhibited typical symptoms of PD. The number of TH-positive neurons and expression level of TH in the model group were significantly reduced in the substantia nigra by about 65% and 75% (P<0.001) 7 days after the fifth injection of MPTP. The number of COX-2-immunoreactive cells and the expression level of COX-2 were significantly increased. P-c-Jun was specifically expressed in the nuclei of neurons and p-c-Jun expression level was significantly increased in the SN 6 h after the third injection of MPTP. Double-labeling immunofluorescence assay showed coexpression of COX-2 and p-c-Jun in TH-positive neurons in the SN. In mice treated with JNK inhibitor, the number of TH-positive neurons and TH expression level in the SN was only decreased by 15% and 20% as compared with the control group (P<0.001) 7 days after the fifth injection of MPTP, COX-2-positive cell number and COX-2 expression level were obviously reduced as compared with the model group (P<0.001), and p-c-Jun was expressed mainly in the cytoplasm of the neurons whose expression level in SN were significantly decreased 6 h after the third injection of MPTP. The PD mice treated with SP600125 showed slight behavioral symptoms.
CONCLUSIONP-c-Jun expression may play an important role in mediating COX-2 expression in the SN in the MPTP model of subacute PD, and inhibiting p-c-Jun activity may provide neuroprotection to the mouse model.
