AUTHOR=Wang Chunfei , Feng Liang , Ma Liang , Chen Haifeng , Tan Xiaobin , Hou Xuefeng , Song Jie , Cui Li , Liu Dan , Chen Juan , Yang Nan , Wang Jing , Liu Ying , Zhao Bingjie , Wang Gang , Zhou Yuanli , Jia Xiaobin 

TITLE=Alisol A 24-Acetate and Alisol B 23-Acetate Induced Autophagy Mediates Apoptosis and Nephrotoxicity in Human Renal Proximal Tubular Cells

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 8 - 2017

YEAR=2017

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2017.00172

DOI=10.3389/fphar.2017.00172

ISSN=1663-9812

ABSTRACT=In the present study, we explored whether alisol A 24-acetate (24A) and alisol B 23-acetate (23B) induced autophagy accompanied with apoptosis and nephrotoxicity via PI3K/Akt/mTOR signaling pathway in HK-2 cells. Importantly, the protein expression and mRNA level of Clusterin, Kim-1 and TFF-3 could be significantly increased by 23B (15 μM) and 24A (6 μM), which was a speculation of nephrotoxicity connected with HE staining of rat kidneys. The results showed that autophagy could be induced by both 23B and 24A in HK-2 cells via significantly enhancing the ratio of LC3II/LC3I, the protein expression of Beclin-1 as well as the mRNA level of LC3 and Beclin-1. Furthermore, cell apoptosis could be triggered by 23B and 24A via significantly decreasing the protein expression and mRNA level of Bcl-2 and Bcl-xl. An autophagy inhibitor, 3-methyladenine, could partially reverse cell viability and conversely change the ratio of LC3II/LC3I and the protein expression of Bcl-2 and Kim-1. Meanwhile, PI3K/Akt/mTOR signaling pathway could be inhibited by 23B and 24A. Thus this study helped to understand that 23B and 24A induced autophagy possibly resulted in apoptosis and nephrotoxicity through PI3K/Akt/mTOR signaling pathway and would facilitate further studies for Rhizoma alismatis nephrotoxicity.