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Cholesterol Retards Senescence in Bone Marrow Mesenchymal Stem Cells by Modulating Autophagy and ROS/p53/p21(Cip1/Waf1) Pathway

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 and...

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Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5040816/
https://www.ncbi.nlm.nih.gov/pubmed/27703600
http://dx.doi.org/10.1155/2016/7524308
Descripción
Sumario: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 and p21(Cip1/Waf1) 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 H(2)O(2) and the 3rd passage BMSCs. Moreover, CH inhibited the production of ROS and expression of p53 and p21(Cip1/Waf1) 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/p21(Cip1/Waf1) signaling pathway.