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Protective effect of simvastatin on impaired intestine tight junction protein ZO-1 in a mouse model of Parkinson’s disease

Journal of Huazhong University of Science and Technology [Medical Sciences] volume 35, pages 880–884 (2015)Cite this article

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.

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Affiliations

  1. Department of Neurology, the First Affiliated Hospital of Nanchang University, Nanchang, 330006, China

    Xin Fang & Ren-shi Xu

Authors
  1. Xin Fang
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  2. Ren-shi Xu
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Correspondence to Xin Fang.

Additional information

This project was supported by grants from the Natural Science Foundation of Jiangxi Province (No. 20142BAB205092), Foundation of Jiangxi Educational Committee for Youths (No. GJJ13030) and Jiangxi Province Science Foundation for Youths (No. 20132BAB215037).

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Fang, X., Xu, Rs. Protective effect of simvastatin on impaired intestine tight junction protein ZO-1 in a mouse model of Parkinson’s disease. J. Huazhong Univ. Sci. Technol. [Med. Sci.] 35, 880–884 (2015). https://doi.org/10.1007/s11596-015-1522-2

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  • DOI: https://doi.org/10.1007/s11596-015-1522-2

Key words

  • duodenum
  • colon
  • simvastatin
  • tight junction protein
  • matrix metallopeptidase 9