Protective role of autophagy in triptolide-induced apoptosis of TM3 Leydig cells

Abstract

Background and Objectives Triptolide (TP) is known to impair testicular development and spermatogenesis in mammals, but the mechanism of the side effects still needs to be investigated. The aim of the research is to confirm whether TP can cause autophagy in TM3 Leydig cells and the potential molecular pathway in vitro. Methods TM3 Leydig cells are used to investigate the molecular pathway through Western blot, detection of apoptosis, transmission electron microscopy for autophagosomes and so on. Results The data show that TP treatment resulted in the decreasing of the viability of TM3 cells due to the increased apoptosis. Treated with TP, the formation of autophagosomes, the decrease in P62, and the increase in the conversion of LC3-I to LC3-II suggested the induction of autophagy. The induction of autophagy has accompanied the activation of the mTOR/P70S6K signal pathway. The viability of the TM3 cells was further inhibited when they were co-treated with autophagy inhibitor, chloroquine (CQ). Conclusion All these data suggest that autophagy plays a very important role in antagonizing TM3 cell apoptosis during the TP exposure.

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“…Our experimental results also confirmed that the changes in the levels of these two proteins during the inhibition of tumor development by niclosamide were consistent with previous studies. There is also some evidence for the ability of niclosamide to suppress colon cancer cell growth via inducing the formation of autophagosomes 38 , 39 . As such, this drug may engage a range of context-specific mechanisms to exert its antitumor effects, emphasizing the need for further research focused on these topics.…”

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“…Extensive research has illuminated autophagy's multifaceted regulation, involving an intricate interplay between inflammation and apoptosis. [22][23][24] In macrophages, autophagy induction has been proposed to exert an anti-inflammatory effect, while inhibition of autophagy has been linked to enhanced apoptosis. 25,26 Many studies have indicated that autophagy takes part in the recovery of kidney during AKI.…”