Pseudolaric Acid B–Induced Autophagy Contributes to Senescence via Enhancement of ROS Generation and Mitochondrial Dysfunction in Murine Fibrosarcoma L929 Cells

Journal of Pharmacological Sciences

Simiao Fan¹  Satoshi Onodera³  Zhao Li¹  Takashi Ikejima¹  Mingyu Xia¹  Guodong Yao¹  Shin-ichi Tashiro²  Min Qi¹  Haiyan Zhou¹ 

[1] China-Japan Research Institute of Medical and Pharmaceutical Sciences, Shenyang Pharmaceutical University, China;Institute for Clinical and Biomedical Sciences, Japan;Department of Clinical and Biomedical Sciences, Showa Pharmaceutical University, Japan

关键词: pseudolaric acid B;    senescence;    autophagy;    reactive oxygen species (ROS);    mitochondrial dysfunction;   

DOI  :  10.1254/jphs.12269FP

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(35)Cited-By(8)Pseudolaric acid B (PAB) is the primary biologically active compound isolated from the root bark of P. kaempferi Gordon. Our previous study demonstrated that PAB induced mitotic catastrophe in L929 cells and indicated that only a small percentage (12%) of the cells undergoing mitotic catastrophe displayed an apoptotic phenotype after PAB treatment for 72 h. In this study, we found that a minority of the cells undergoing mitotic catastrophe ended in apoptosis, and a majority of them entered a period of senescence. Further data confirmed that PAB induced autophagy, reactive oxygen species (ROS) generation, and mitochondrial dysfunction in L929 cells. Subsequently, we found that autophagy inhibitors significantly delayed the senescence process, indicating that autophagy facilitated senescence. Moreover, ROS scavenger significantly decreased the autophagic level and improved mitochondrial function. Additionally, autophagy inhibitors effectively reduced ROS levels and ameliorated mitochondrial function. In conclusion, autophagy promoted senescence via enhancement of ROS generation and mitochondrial dysfunction in PAB-treated L929 cells.

【 授权许可】

Unknown