Protective effect of simvastatin on impaired intestine tight junction protein ZO-1 in a mouse model of Parkinson's disease / 华中科技大学学报(医学)(英德文版)
Journal of Huazhong University of Science and Technology (Medical Sciences)
; (6): 880-884, 2015.
Article
in En
| WPRIM
| ID: wpr-250326
Responsible library:
WPRO
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.
Key words
Full text:
1
Index:
WPRIM
Main subject:
Parkinson Disease
/
Pharmacology
/
Hydroxymethylglutaryl-CoA Reductase Inhibitors
/
Simvastatin
/
Disease Models, Animal
/
Zonula Occludens-1 Protein
/
Metabolism
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Journal of Huazhong University of Science and Technology (Medical Sciences)
Year:
2015
Type:
Article