title: Protective effect of simvastatin on impaired intestine tight junction protein ZO-1 in a mouse model of Parkinson's disease.
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.
authors.affiliation: Department of Neurology, the First Affiliated Hospital of Nanchang University, Nanchang, 330006, China. fangx2011@163.com.
authors.forename: Xin
authors.initials: X
authors.lastname: Fang
authors.affiliation: Department of Neurology, the First Affiliated Hospital of Nanchang University, Nanchang, 330006, China.
authors.forename: Ren-Shi
authors.initials: RS
authors.lastname: Xu
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D051379:Mice; D010300:Parkinson Disease / Q000378:metabolism*; D019821:Simvastatin / Q000494:pharmacology*; D062826:Zonula Occludens-1 Protein / Q000187:drug effects*
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; C569043:Tjp1 protein, mouse; D062826:Zonula Occludens-1 Protein; D019821:Simvastatin
keywords: colon; duodenum; matrix metallopeptidase 9; simvastatin; tight junction protein