EGCG对富亮氨酸重复激酶2活性的影响及其作用机制

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Abstract Objective: To study the effect of epigallocatechin3gallate (EGCG) on leucine rich repeat kinase 2 (LRRK2) activities in Drosophila model and its potential molecular mechanism. Methods: DdcLRRK2G2019S strains of Drosophila was selected and divided into 7 groups. The control group was fed with standard corn medium. The Drosophila of each experimental group were fed with medium containing GW5074, NAC and EGCG with concentrations of 0.1, 1, 10 and 100 μmol/L, respectively. The life span and motor function of Drosophila were tested and screened for the optimal concentration and optimal time of drug action.Western blotting was used to detect pLRRK2, pp38 MAPK, nuclear factor erythroid 2related factor 2(Nrf2), pERK1/2 and tyrosine hydroxylase(TH) protein expressions in Drosophila brain tissues. Results: Compared with the control group, both 10 μmol/L EGCG group and 1 μmol/L EGCG group had significantly prolonged the lifespan and improved the motor function of Drosophila(P<0.05), while the effect of 0.1 μmol/L EGCG and 100 μmol/L EGCG group was not significant; there were marked differences in the behavioral changes of Drosophila in the 5th week(P<0.05). Compared with the control group, 10 μmol/L and 1 μmol/L EGCG group showed significantly higher expression of Nrf2, pERK1/2 and lower expression of pLRRK2, pp38 MAPK(P<0.05). Conclusion: EGCG might effectively inhibit LRRK2 kinase activity through signaling pathways such as Keap1Nrf2ARE and MAPK.

Received: 18 May 2018

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http://zzs.ujs.edu.cn/xbyxb/EN/ OR http://zzs.ujs.edu.cn/xbyxb/EN/Y2018/V28/I05/397

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