Cholesterol Retards Senescence in Bone Marrow Mesenchymal Stem Cells by Modulating Autophagy and ROS/p53/p21Cip1/Waf1 Pathway. (15th September 2016)

• Record Type: Journal Article
• Authors: Zhang, Mingyu; Du, Yue; Lu, Renzhong; Shu, You; Zhao, Wei; Li, Zhuoyun; Zhang, Yu; Liu, Ruixue; Yang, Ti; Luo, Shenjian; Gao, Ming; Zhang, Yue; Zhang, Guiye; Liu, Jiaqi; Lu, Yanjie
• Other Names: Pallottini Valentina Academic Editor.
• Is Part Of: Oxidative medicine and cellular longevity. Volume 2016(2016)
• Publication Date: 2016-09-15
• Subjects: Oxidative stress -- Periodicals; Cells -- Aging -- Periodicals; Cells -- Aging; Oxidative stress; Oxidative Stress -- Periodicals; Cell Aging -- Periodicals; Periodicals; 611.0181
• DOI: 10.1155/2016/7524308
• Languages: English
• ISSNs: 1942-0900

Abstract

Abstract : In the present study, we demonstrated that bone marrow mesenchymal stem cells (BMSCs) of the 3rd passage displayed the senescence-associated phenotypes characterized with increased activity of SA- β -gal, altered autophagy, and increased G1 cell cycle arrest, ROS production, and expression of p53 andp 21 C i p 1 / W a f 1 compared with BMSCs of the 1st passage. Cholesterol (CH) reduced the number of SA- β -gal positive cells in a dose-dependent manner in aging BMSCs induced by H2 O2 and the 3rd passage BMSCs. Moreover, CH inhibited the production of ROS and expression of p53 andp 21 C i p 1 / W a f 1 in both cellular senescence models and decreased the percentage of BMSCs in G1 cell cycle in the 3rd passage BMSCs. CH prevented the increase in SA- β -gal positive cells induced by RITA (reactivation of p53 and induction of tumor cell apoptosis, a p53 activator) or 3-MA (3-methyladenine, an autophagy inhibitor). Our results indicate that CH not only is a structural component of cell membrane but also functionally contributes to regulating cellular senescence by modulating cell cycle, autophagy, and the ROS/p53/p 21 C i p 1 / W a f 1 signaling pathway.