[Effect of phosphorylated c-Jun expression on COX-2 expression in the substantia nigra of MPTP mouse model of subacute Parkinson disease].
OBJECTIVE
To 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.


METHODS
C57BL/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.


RESULTS
Compared 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.


CONCLUSIONS
P-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.
Wang
Yong-Sheng
YS
Department of Anatomy, North China Coal Medical College, Tangshan 063000, China. TSW406@163.com
Zhou
Jian-Ping
JP
Wei
Zi-Feng
ZF
Tian
Qing-You
QY
Zhou
Hong-Xia
HX
Zhang
Yu-Xin
YX
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology*; D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D015153:Blotting, Western; D016923:Cell Death / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000473:pathology; D010300:Parkinson Disease / Q000201:enzymology / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism*
D000873:Anthracenes; D010750:Phosphoproteins; D016755:Proto-Oncogene Proteins c-jun; C432165:pyrazolanthrone; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D051546:Cyclooxygenase 2; D004298:Dopamine