Excessive misfolded proteins and/or dysfunctional mitochondria, which may cause energy deficiency, have been implicated in the etiopathogenesis of Parkinson’s disease (PD). Enhanced clearance of misfolded proteins or injured mitochondria via autophagy has been reported to have neuroprotective roles in PD models. The fact that resveratrol is a known compound with multiple beneficial effects similar to those associated with energy metabolism led us to explore whether neuroprotective effects of resveratrol are related to its role in autophagy regulation. We tested whether modulation of mammalian silent information regulator 2 (SIRT1) and/or metabolic energy sensor AMP-activated protein kinase (AMPK) are involved in autophagy induction by resveratrol, leading to neuronal survival. Our results showed that resveratrol protected against rotenone-induced apoptosis in SH-SY5Y cells and enhanced degradation of α-synucleins in α-synuclein-expressing PC12 cell lines via autophagy induction. We found that suppression of AMPK and/or SIRT1 caused decrease of protein level of LC3-II, indicating that AMPK and/or SIRT1 are required in resveratrol-mediated autophagy induction. Moreover, suppression of AMPK caused inhibition of SIRT1 activity and attenuated protective effects of resveratrol on rotenone-induced apoptosis, further suggesting that AMPK-SIRT1-autophagy pathway plays an important role in the neuroprotection by resveratrol on PD cellular models.
Scope: The accumulation of misfolded α-synuclein in dopaminergic neurons is the leading cause of Parkinson’s disease (PD). Resveratrol (RV), a polyphenolic compound derived from grapes and red wine, exerts a wide range of beneficial effects via activation of sirtuin 1 (SIRT1) and induction of vitagenes. Here, we assessed the role of RV in a 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) induced mouse model of PD and explored its potential mechanisms. Methods and results: RV and EX527, a specific inhibitor of SIRT1, were administered before and after MPTP treatment. RV protected against MPTP-induced loss of dopaminergic neurons, and decreases in tyrosine hydroxylase and dopamine levels, as well as behavioral impairments. Meanwhile, RV administration activated SIRT1. Microtubule-associated protein 1 light chain 3 (LC3) was then deacetylated and redistributed from the nucleus to the cytoplasm, which provoked the autophagic degradation of α-synuclein in dopaminergic neurons. Furthermore, EX527 antagonized the neuroprotective effects of RV by reducing LC3 deacetylation and subsequent autophagic degradation of α-synuclein. Conclusion: We showed that RV ameliorated both motor deficits and pathological changes in MPTP-treated mice via activation of SIRT1 and subsequent LC3 deacetylation-mediated autophagic degradation of α-synuclein. Our observations suggest that RV may be a potential prophylactic and/or therapeutic agent for PD.
Fusarium wilt of watermelon, caused by F. oxysporum f.sp. niveum (FON), is a devastating disease that causes extensive losses throughout the world. Five bacterial strains (L3, h, β, b, and L) isolated from the watermelon rhizosphere showed antagonistic activity against FON during in vitro tests. Strain L3 produced diffusible and volatile organic compounds (VOCs) which showed the strongest antifungal activity. Arabidopsis thaliana plantlets exposed to VOCs produced by strain L3 showed a 2.39‐fold increase in biomass, 1.40‐fold increase in primary root length, and 5.05‐fold increase in number of lateral roots. Confocal laser scanning microscope showed that the GFP‐labeled strain L3 could colonize along the elongation and differentiation zones of watermelon roots. In greenhouse pot experiments, the biocontrol efficiency of strain L3 against fusarium wilt of watermelon was up to 68.4% in comparison with the control treatment. In addition, inoculation of the strain L3 resulted in a 23.4% increase in plant fresh weight. Based on 16S rDNA sequence analysis, the strain L3 was identified as Bacillus amyloliquefaciens L3. Fourteen VOCs produced by strain L3 were identified through GC‐MS analysis. Of nine VOCs tested, 2‐nonanone and 2‐heptanone were proved to have strong antifungal properties. Acetoin and 2,3‐butanediol were found to promote plant growth. The results suggested B. amyloliquefaciens L3 was a potential biocontrol agent, and that VOCs produced by B. amyloliquefaciens L3 play important roles in the process of biocontrol and plant growth promotion.
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