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The Mechanism By Which Selenium Compounds Affect Cell Senescence And Death Noni Juice Extract Protects Nerve Cells

Posted on:2019-03-06Degree:MasterType:Thesis
Country:ChinaCandidate:X ShiFull Text:PDF
GTID:2434330572453385Subject:Microbial and Biochemical Pharmacy
Abstract/Summary:PDF Full Text Request
Aging of the population is a global problem,and cellular oxidative damage causes aging of the human body,which leads to a significant increase in the incidence of geri-atric diseases.Therefore,actively exploring natural anti-oxidants and studying related mechanisms will help us to prevent and treat geriatric diseases.This dissertation fo-cuses on the antioxidative mechanism of selenium compounds and noni juice extracts to provide theoretical basis for related applications.The first part of this research paper is to study the anti-senescence mechanism of selenium-enriched malt powder(WSM).H2O2 was used to establish the aging model on human lung embryonic fibroblast cells,and we detected that a lower concentration of WSM can promote cell proliferation.Its mechanisms are involved with reduction of ROS level,mitigation of H2O2-induced retardation of cell cycle,decrease of ag-ing-related protein p21 expression and then reduction of the number of senescent cells.The second part mainly studies the mechanism of the selenium metabolite methyl selenate(MSA)on human lung-derived normal MRC-5 cells and small cell lung can-cer A549 cells.The results demonstrated that MSA induced apoptosis in MRC-5 cells and caused cell senescence at low concentrations,while the death and the senescence cells were not obviously observed in A549 cells treatment with the same concentration of MSA.The mechanism is that MSA induced the rise of Nrf2 protein in the course of endoplasmic reticulum stress in MRC-5 cells and then decreased,while A549 cells showed a significant decrease.The levels of p53 protein increased during MRC-5 apoptosis but decreased on A549 cells.In addition,a moderate concentration of MSA had a transient inhibitory effect on A549 cells and then cells reattached and restored proliferation.This mechanism is related to endogenous levels of Nrf2 in cells.There are similar phenomena when MSA treated human breast cancer MCF-7 and the drug-resistant strain cells which express high endogenous levels of Nrf2.The last part,the neuroprotective effect and mechanism of noni juice extracts against TBHP-induced SH-SY5Y cells damage were investigated.The results demon-strated that noni juice protected SH-SY5Y cells against TBHP-induced oxidative stress and the associated apoptosis effectively,reduced the TBHP-induced ROS generation and mitochondrial membrane depolarization,restored cellular antioxidant enzymes activity,up-regulated expressions of HO-1,CAT and SOD-1 and increased the nuclear accumulation of Nrf2.These results suggested that noni juice can effectively protect cell damage caused by TBHP.Our study first time confirmed that WSM had obvious anti-aging effects and the mechanisms of MSA in tumor cells and normal cells are different,and it is related to the anti-oxidation Nrf2 protein and tumor suppressor gene p53.Furthermore,we de-tected that MSA treatment of tumor cells restored the proliferation.This study further elucidated the mechanism of antioxidative damage of selenium compounds and noni juice extracts,providing a theoretical basis for improving the health of the elderly and preventing related diseases.
Keywords/Search Tags:selenium compounds, cell senescence, endoplasmic reticulum stress, Nrf2 protein, noni juice
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