Protective effect of simvastatin on impaired intestine tight junction protein ZO-1 in a mouse model of Parkinson's disease.
10.1007/s11596-015-1522-2
- Author:
Xin FANG
1
;
Ren-shi XU
2
Author Information
1. Department of Neurology, the First Affiliated Hospital of Nanchang University, Nanchang, 330006, China. fangx2011@163.com.
2. Department of Neurology, the First Affiliated Hospital of Nanchang University, Nanchang, 330006, China.
- Publication Type:Journal Article
- Keywords:
colon;
duodenum;
matrix metallopeptidase 9;
simvastatin;
tight junction protein
- MeSH:
Animals;
Disease Models, Animal;
Hydroxymethylglutaryl-CoA Reductase Inhibitors;
pharmacology;
Mice;
Parkinson Disease;
metabolism;
Simvastatin;
pharmacology;
Zonula Occludens-1 Protein;
drug effects
- From:
Journal of Huazhong University of Science and Technology (Medical Sciences)
2015;35(6):880-884
- CountryChina
- Language:English
-
Abstract:
Recently, several studies showed that gastrointestinal tract may be associated with pathophysiology of Parkinson's disease (PD). Intestine tight junction protein zonula occluden-1 (ZO-1) is an important component of intestinal barrier which can be degraded by matrix metallopeptidase 9 (MMP-9). In our previous study, a significant decline in ZO-1 was observed along with enhanced MMP-9 activity in the duodenum and distal colon of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-intoxicated mice. In this study, the protective effect of simvastatin on ZO-1 was investigated using an MPTP mouse model of PD. Seven days after the end of MPTP application, the expression level of ZO-1 was evaluated by immunohistochemistry. The protein expression levels of ZO-1 and MMP9 were detected by Western blotting. Meanwhile, MMP-9 activity was analyzed by gelatin zymography. MPTP treatment led to a decrease in the expression of ZO-1, which was accompanied by elevated MMP-9 activity. Treatment with simvastatin could partly reverse the MPTP-induced changes in ZO-1 expression and reduce MMP-9 protein and activity. Taken together, these findings suggest that simvastatin administration may partially reverse the impairment of ZO-1 induced by MPTP via inhibiting the activity of MMP9, fortify the impaired intestinal barrier and limit gut-derived toxins that pass across the intestinal barrier.
