文献类型：期刊文献

英文题名：Lactose induced redox-dependent senescence and activated Nrf2 pathway

作者：Xing, Shuli[1];Zhang, Lanxin[1];Lin, Huiling[1];Mao, Zhifan[1];Bao, Keting[1];Hao, Peng[3];Pei, Zhe[3];Li, Jian[2];Hu, Zelan[1]

机构：[1]East China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab New Drug Design, 130 Mei Long Rd, Shanghai 200237, Peoples R China;[2]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, 130 Mei Long Rd, Shanghai 200237, Peoples R China;[3]Duke Univ, Sch Med, Durham, NC USA

年份：2019

卷号：12

期号：6

起止页码：2034

外文期刊名：INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000473287100010)】；

基金：This work was supported by the Exploratory Research Foundation of ECUST (Grant number: 222201714058) and National Natural Science Foundation of China (Grant number: 8177-2689).

语种：英文

外文关键词：Lactose; ROS; oxidative stress; cellular senescence; Nrf2

摘要：Lactose is a disaccharide found in milk and thus a part of our daily food intake. Upon ingestion, it is hydrolyzed to glucose and galactose by the enzyme lactase and absorbed in the small intestine. People who suffer from lactose intolerance are unable to completely digest it due to deficiency of lactase, leading to intestinal problems such as diarrhoea, and bloating. Various studies have focused on treating these symptoms. However, the effects of lactose that diffuses passively into cells, on cellular senescence have largely remained unknown. Thus, the present study investigated the effects and mechanisms of lactose on senescence both in vitro and in vivo. The study was conducted in MRC-5 cells. The cellular senescence was estimated by determining the expression of SA-beta-gal and p16(ink4a). The cell viability of MRC-5 cells was determined by the CCK-8 Assay. Activity of intracellular reactive oxygen species was estimated by measuring the levels of superoxide dismutase (SOD), glutathione (GHS), and reactive oxygen species (ROS). The mechanism of lactose on cellular senescence was explored by western blotting. We also studied the effect of lactose on the lifespan of Caenorhabditis elegans. Increased activities of SA-beta-gal and p16(ink4a) revealed the ability of lactose to induce senescence in MRC-5 cells. The elevated intracellular ROS level and decreased GSH and SOD levels in these cells were indicative of cellular oxidative stress induced by lactose. Furthermore, western blotting analysis of Nrf2 and mRNA expression of its downstream genes suggested the Nrf2/ARE pathway was involved in the oxidative stress induced by lactose. These results were further validated by the shortened lifespan of C. elegans after lactose supplement. Moreover, the lactose-induced senescence could be alleviated by an antioxidant, N-Acetyl-L-cysteine (NAC), both in vitro and in vivo. The present study observed a positive correlation between lactose and cellular oxidative stress, suggesting the latter to be an underlying mechanism of lactose-induced senescence.