Neuroprotective Effects of Palmatine via the Enhancement of Antioxidant Defense and Small Heat Shock Protein Expression in Aβ-Transgenic Caenorhabditis elegans
| Autor: | Xiongming Luo, Qiong Cheng, Qiong Peng, Aimin Qiao, Ying Wang, Jing Zhang, Qina Su, Weizhang Jia |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Aging
Article Subject Berberine Alkaloids medicine.disease_cause Biochemistry Neuroprotection Antioxidants Animals Genetically Modified chemistry.chemical_compound Alzheimer Disease Heat shock protein medicine Animals Humans Caenorhabditis elegans Caenorhabditis elegans Proteins chemistry.chemical_classification Reactive oxygen species Amyloid beta-Peptides QH573-671 Chemistry Neurotoxicity Lipid metabolism Palmatine Cell Biology General Medicine medicine.disease Cell biology Heat-Shock Proteins Small Oxidative Stress Neuroprotective Agents Toxicity Reactive Oxygen Species Cytology Oxidative stress Research Article |
| Zdroj: | Oxidative Medicine and Cellular Longevity, Vol 2021 (2021) Oxidative Medicine and Cellular Longevity |
| ISSN: | 1942-0994 1942-0900 |
| Popis: | Palmatine is a naturally occurring isoquinoline alkaloid that has been reported to display neuroprotective effects against amyloid-β- (Aβ-) induced neurotoxicity. However, the mechanisms underlying the neuroprotective activities of palmatine remain poorly characterized in vivo. We employed transgenic Caenorhabditis elegans models containing human Aβ1-42 to investigate the effects and possible mechanisms of palmatine-mediated neuroprotection. Treatment with palmatine significantly delayed the paralytic process and reduced the elevated reactive oxygen species levels in Aβ-transgenic C. elegans. In addition, it increased oxidative stress resistance without affecting the lifespan of wild-type C. elegans. Pathway analysis suggested that the differentially expressed genes were related mainly to aging, detoxification, and lipid metabolism. Real-time PCR indicated that resistance-related genes such as sod-3 and shsp were significantly upregulated, while the lipid metabolism-related gene fat-5 was downregulated. Further studies demonstrated that the inhibitory effects of palmatine on Aβ toxicity were attributable to the free radical-scavenging capacity and that the upregulated expression of resistance-related genes, especially shsp, whose expression was regulated by HSF-1, played crucial roles in protecting cells from Aβ-induced toxicity. The research showed that there were significantly fewer Aβ deposits in transgenic CL2006 nematodes treated with palmatine than in control nematodes. In addition, our study found that Aβ-induced toxicity was accompanied by dysregulation of lipid metabolism, leading to excessive fat accumulation in Aβ-transgenic CL4176 nematodes. The alleviation of lipid disorder by palmatine should be attributed not only to the reduction in fat synthesis but also to the inhibition of Aβ aggregation and toxicity, which jointly maintained metabolic homeostasis. This study provides new insights into the in vivo neuroprotective effects of palmatine against Aβ aggregation and toxicity and provides valuable targets for the prevention and treatment of AD. |
| Databáze: | OpenAIRE |
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