文献类型：期刊文献

英文题名：The ROS-mediated activation of IL-6/STAT3 signaling pathway is involved in the 27-hydroxycholesterol-induced cellular senescence in nerve cells

作者：Liu, Jiao[1];Liu, Yun[1];Chen, Juan[1];Hu, Chunyan[1];Teng, Mengying[1];Jiao, Kailin[1];Shen, Zhaoxia[1];Zhu, Dongmei[1];Yue, Jia[2];Li, Zhong[1];Li, Yuan[1]

第一作者：Liu, Jiao

通信作者：Li, Z[1];Li, Y[1]

机构：[1]Nanjing Med Univ, Sch Publ Hlth, Dept Nutr & Food Hyg, Nanjing 211166, Jiangsu, Peoples R China;[2]Gansu Univ Chinese Med, Sch Publ Hlth, Dept Nutr & Food Hyg, Lanzhou 730000, Gansu, Peoples R China

第一机构：Nanjing Med Univ, Sch Publ Hlth, Dept Nutr & Food Hyg, Nanjing 211166, Jiangsu, Peoples R China

通信机构：[1]corresponding author), Nanjing Med Univ, Sch Publ Hlth, Dept Nutr & Food Hyg, Nanjing 211166, Jiangsu, Peoples R China.

年份：2017

卷号：45

起止页码：10

外文期刊名：TOXICOLOGY IN VITRO

收录：;Scopus(收录号：2-s2.0-85027861234);WOS:【SCI-EXPANDED(收录号:WOS:000419413400003)】；

基金：This work was supported by National Natural Science Foundation of China (81171987 and 81673205), the Major Program of Natural Science Research of Jiangsu Higher Education Institutions (15KJA330001), the Research Fund for the Doctoral Program of Higher Education of China (20133234110007), and the project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).

语种：英文

外文关键词：27-Hydroxycholesterol; Cellular senescence; Reactive oxygen species; Signal transducer and activator of transcription 3

摘要：The oxysterol 27-hydroxycholesterol (27HC) is a selective estrogen receptor modulator (SERMs), which like endogenous estrogen 17 beta-estradiol (E-2) induces the proliferation of ER-positive breast cancer cells in vitro. Interestingly, the observation that 27HC induces adverse effects in neural system, distinguishing it from E-2. It has been suggested that high levels of circulating cholesterol increase the entry of 27HC into the brain, which may induce learning and memory impairment. Based on this evidence, 27HC may be associated with neurodegenerative processes and interrupted cholesterol homeostasis in the brain. However, the biological events that participate in this process remain largely elusive. In the present study, we demonstrated that 27HC induced apparent cellular senescence in nerve cells. Senescence-associated beta-galactosidase (SA-beta-Gal) assay revealed that 27HC induced senescence in both BV2 cells and PC12 cells. Furthermore, we demonstrated that 27HC promoted the accumulation of cellular reactive oxygen species (ROS) in nerve cells and subsequently activation of IL-6/STAT3 signaling pathway. Notably, treatment with the ROS scavenger N-acetylcysteine (NAC) markedly blocked 27HC-induced ROS production and activation of IL-6/STAT3 signaling pathway. Either blocking the generation of ROS or inhibition of IL-6/STAT3 both attenuated 27HC-induced cellular senescence. In sum, these findings not only suggested a mechanism whereby 27HC induced cellular senescence in nerve cells, but also helped to recognize the 27HC as a novel harmful factor in neurodegenerative diseases.