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槲皮素保护酵母酿酒酵母pep4突变体免受氧化和凋亡应激并延长时序寿命。

Quercetin Protects Yeast Saccharomyces cerevisiae pep4 Mutant from Oxidative and Apoptotic Stress and Extends Chronological Lifespan.

作者信息

Alugoju Phaniendra, Janardhanshetty Sudharshan Setra, Subaramanian Subasri, Periyasamy Latha, Dyavaiah Madhu

机构信息

Department of Biochemistry and Molecular Biology, Pondicherry University, Pondicherry, 605 014, India.

DBT-IPLS program, School of Life Sciences, Pondicherry University, Pondicherry, 605 014, India.

出版信息

Curr Microbiol. 2018 May;75(5):519-530. doi: 10.1007/s00284-017-1412-x. Epub 2017 Dec 9.

Abstract

The yeast Saccharomyces cerevisiae PEP4 gene encodes vacuolar endopeptidase proteinase A (Pep4p), which is a homolog of the human CTSD gene that encodes cathepsin D. Mutation of CTSD gene in human resulted in a number of neurodegenerative diseases. In this study, we have shown that yeast pep4 mutant cells are highly sensitive to oxidative and apoptotic stress induced by hydrogen peroxide and acetic acid, respectively. pep4∆ cells also showed accumulation of reactive oxygen species (ROS), apoptotic markers, and reduced chronological lifespan. In contrast, quercetin pretreatment protected the pep4 mutant from oxidative and apoptotic stress-induced sensitivity by scavenging ROS and reducing apoptotic markers. The percentage viability of quercetin-treated pep4∆ cells was more pronounced and increased stress resistance against oxidant, apoptotic, and heat stress during chronological aging. From our experimental results, we concluded that quercetin protects yeast pep4 mutant cells from oxidative stress and apoptosis, thereby increasing viability during chronological aging.

摘要

酿酒酵母(Saccharomyces cerevisiae)的PEP4基因编码液泡内肽酶蛋白酶A(Pep4p),它是人类CTSD基因的同源物,CTSD基因编码组织蛋白酶D。人类CTSD基因突变会导致多种神经退行性疾病。在本研究中,我们发现酵母pep4突变体细胞分别对过氧化氢和乙酸诱导的氧化应激和凋亡应激高度敏感。pep4∆细胞还表现出活性氧(ROS)、凋亡标志物的积累以及时序寿命缩短。相比之下,槲皮素预处理通过清除ROS和减少凋亡标志物,保护pep4突变体免受氧化应激和凋亡应激诱导的敏感性。槲皮素处理的pep4∆细胞的存活率百分比更显著,并且在时序衰老过程中增强了对氧化、凋亡和热应激的抗性。根据我们的实验结果,我们得出结论,槲皮素保护酵母pep4突变体细胞免受氧化应激和凋亡,从而在时序衰老过程中提高存活率。

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