Fangchinoline accumulates autophagosomes by inhibiting autophagic degradation and promoting TFEB nuclear translocation

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	Fangchinoline accumulates autophagosomes by inhibiting autophagic degradation and promoting TFEB nuclear translocation
	Tang, ZH; Guo, X; Cao, WX; Chen, X. P.; Lu, J.
	2017-08-01
Source Publication	16th Meeting of Consortium for Globalization of Chinese Medicine
Abstract	Autophagy, an evolutionarily conserved cellular self-digestive process, is associated with different diseases and can be inhibited or induced by a series of agents. In this study, we reported that fangchinoline (FCL), an alkaloid from Stephania tetrandra S. Moore, increased the expression of LC3-II and the formation of GFP-LC3 puncta in concentration- and time-dependent manners in A549 cells. The FCL-increased expression of LC3-II was not further increased under co-treatment with bafilomycin A1, an autophagy inhibitor, and numerous yellow puncta were observed in A549 mRFP-EGFP-LC3 stable cells under FCL treatment, suggesting that FCL inhibits autophagic flux. Results of co-localization of GFP-LC3 with lysosome tracker red or lysosomal-associated membrane protein 1 indicated that FCL inhibits autophagosomes-lysosomes fusion. Furthermore, FCL decreased the activities of cathepsins B and D and affected cellular acidification. Interestingly, FCL also increased the nuclear translocation of transcription factor EB (TFEB), a master regulator of autophagic and lysosomal genes, and the mRNA expressions of TFEB-targeted genes, such as SQSTM1, MAP1LC3B, and UVRAG. Knockdown of TFEB by using small inference RNA decreased the FCL-induced expression of LC3-II and the formation of GFP-LC3 puncta. Overall, we report for the first time that FCL increases the expressions of autophagy markers via both inhibition (inhibition of autophagosomes-lysosomes fusion and dysfunction of lysosome) and induction (promotion of TFEB nuclear translocation) of autophagy, providing insights into the better understanding of the complexity of agent-mediated autophagy.
Keyword	Fangchinoline accumulates autophagosomes by inhibiting autophagic degradation and promoting TFEB nuclear translocation
Language	英語English
The Source to Article	PB_Publication
PUB ID	34441
Document Type	Conference paper
Collection	University of Macau
Corresponding Author	Lu, J.
Recommended Citation GB/T 7714	Tang, ZH,Guo, X,Cao, WX,et al. Fangchinoline accumulates autophagosomes by inhibiting autophagic degradation and promoting TFEB nuclear translocation[C], 2017.
APA	Tang, ZH., Guo, X., Cao, WX., Chen, X. P.., & Lu, J. (2017). Fangchinoline accumulates autophagosomes by inhibiting autophagic degradation and promoting TFEB nuclear translocation. 16th Meeting of Consortium for Globalization of Chinese Medicine.

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