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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Front+Pharmacol
2017 ; 8
(ä): 172
Nephropedia Template TP
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Alisol A 24-Acetate and Alisol B 23-Acetate Induced Autophagy Mediates Apoptosis
and Nephrotoxicity in Human Renal Proximal Tubular Cells
#MMPMID28408883
Wang C
; Feng L
; Ma L
; Chen H
; Tan X
; Hou X
; Song J
; Cui L
; Liu D
; Chen J
; Yang N
; Wang J
; Liu Y
; Zhao B
; Wang G
; Zhou Y
; Jia X
Front Pharmacol
2017[]; 8
(ä): 172
PMID28408883
show ga
Two natural compounds alisol A 24-acetate (24A) and alisol B 23-acetate (23B) are
abundant in Rhizoma alismatis. In the present study, we evaluated the induction
of 24A and 23B on apoptosis and possible nephrotoxicity of human renal proximal
tubular (HK-2) cells by activating autophagy and also explored its regulation on
PI3K/Akt/mTOR signaling pathway. Presently, Clusterin, Kim-1, and TFF-3 were
considered to be new bioindicators of nephrotoxicity. Interestingly, the protein
expression and mRNA levels of Clusterin, Kim-1 and TFF-3 could be significantly
increased by 23B and 24A in vivo and in vitro. Furthermore, cell apoptosis could
be triggered by 23B and 24A via significantly decreasing the protein expression
and mRNA levels of Bcl-2 and Bcl-xl. Autophagy of HK-2 cells could be induced by
both 23B and 24A via significantly enhancing the ratio of LC3II/LC3I, the protein
expression of Beclin-1 as well as the mRNA levels of LC3 and Beclin-1. Meanwhile,
PI3K/Akt/mTOR signaling pathway could be inhibited by these two compounds. 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. Thus this study helped to understand that 23B and 24A induced autophagy
resulted in apoptosis and nephrotoxicity through inhibiting PI3K/Akt/mTOR
signaling pathway, facilitating further studies for nephrotoxicity induced by
these two compounds and could be beneficial for safe use of Rhizoma alismatis in
clinic.