Please use this identifier to cite or link to this item:
Title: Induction of autophagy by palmitic acid via protein kinase C-mediated signaling pathway independent of mTOR (mammalian target of rapamycin)
Authors: Tan, S.H.
Shui, G. 
Zhou, J. 
Li, J.J.
Bay, B.-H.
Wenk, M.R.
Shen, H.-M. 
Issue Date: 27-Apr-2012
Citation: Tan, S.H., Shui, G., Zhou, J., Li, J.J., Bay, B.-H., Wenk, M.R., Shen, H.-M. (2012-04-27). Induction of autophagy by palmitic acid via protein kinase C-mediated signaling pathway independent of mTOR (mammalian target of rapamycin). Journal of Biological Chemistry 287 (18) : 14364-14376. ScholarBank@NUS Repository.
Abstract: Lipotoxicity refers to the cytotoxic effects of excess fat accumulation in cells and has been implicated as one of the contributing factors to diseases like obesity, diabetes, and non-alcoholic fatty liver. In this study we sought to examine effects of palmitic acid (PA) and oleic acid, two of the common dietary fatty acids on the autophagic process. We found that PA, but not oleic acid, was able to cause an increase in autophagic flux, evidenced by LC3-II accumulation and formation of GFP-LC3 puncta. Notably, PA-induced autophagy was found to be independent of mTOR regulation. Next, in search of the mechanism mediating PA-induced autophagy, we found increased levels of diacylglycerol species and protein kinase C (PKC) activation in PA-treated cells. More importantly, inhibition of classical PKC isoforms (PKC-α) was able to effectively suppress PA-induced autophagy. Finally, we showed that inhibition of autophagy sensitized the cells to PA-induced apoptosis, suggesting the prosurvival function of autophagy induced by PA. Taken together, results from this study reveal a novel mechanism underlying free fatty acid-mediated autophagy. Furthermore, the pro-survival function of autophagy suggests modulation of autophagy as a potential therapeutic strategy in protection of cells against lipotoxicity and lipid-related metabolic diseases. © 2012 by The American Society for Biochemistry and Molecular Biology, Inc.
Source Title: Journal of Biological Chemistry
ISSN: 00219258
DOI: 10.1074/jbc.M111.294157
Appears in Collections:Staff Publications

Show full item record
Files in This Item:
There are no files associated with this item.

Google ScholarTM



Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.