title: Trehalose, sucrose and raffinose are novel activators of autophagy in human keratinocytes through an mTOR-independent pathway.
abstract: Trehalose is a natural disaccharide that is found in a diverse range of organisms but not in mammals. Autophagy is a process which mediates the sequestration, lysosomal delivery and degradation of proteins and organelles. Studies have shown that trehalose exerts beneficial effects through inducing autophagy in mammalian cells. However, whether trehalose or other saccharides can activate autophagy in keratinocytes is unknown. Here, we found that trehalose treatment increased the LC3-I to LC3-II conversion, acridine orange-stained vacuoles and GFP-LC3B (LC3B protein tagged with green fluorescent protein) puncta in the HaCaT human keratinocyte cell line, indicating autophagy induction. Trehalose-induced autophagy was also observed in primary keratinocytes and the A431 epidermal cancer cell line. mTOR signalling was not affected by trehalose treatment, suggesting that trehalose induced autophagy through an mTOR-independent pathway. mTOR-independent autophagy induction was also observed in HaCaT and HeLa cells treated with sucrose or raffinose but not in glucose, maltose or sorbitol treated HaCaT cells, indicating that autophagy induction was not a general property of saccharides. Finally, although trehalose treatment had an inhibitory effect on cell proliferation, it had a cytoprotective effect on cells exposed to UVB radiation. Our study provides new insight into the saccharide-mediated regulation of autophagy in keratinocytes.
authors.affiliation: Institute of Dermatology, Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Chinese Academy of Medical Science &Peking Union Medical College, Nanjing, 210042, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Chen
authors.affiliation: Institute of Dermatology, Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Chinese Academy of Medical Science &Peking Union Medical College, Nanjing, 210042, China.
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.affiliation: Institute of Dermatology, Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Chinese Academy of Medical Science &Peking Union Medical College, Nanjing, 210042, China.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.affiliation: Institute of Dermatology, Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Chinese Academy of Medical Science &Peking Union Medical College, Nanjing, 210042, China.
authors.forename: Song
authors.initials: S
authors.lastname: Xu
authors.affiliation: Institute of Dermatology, Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Chinese Academy of Medical Science &Peking Union Medical College, Nanjing, 210042, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Huang
authors.affiliation: Institute of Dermatology, Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Chinese Academy of Medical Science &Peking Union Medical College, Nanjing, 210042, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Ju
authors.affiliation: Ontario Cancer Institute, University Health Network, Toronto, Ontario, M5G 2M1, Canada.
authors.forename: Ju
authors.initials: J
authors.lastname: Huang
authors.affiliation: Institute of Dermatology, Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Chinese Academy of Medical Science &Peking Union Medical College, Nanjing, 210042, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Chen
authors.affiliation: Institute of Dermatology, Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Chinese Academy of Medical Science &Peking Union Medical College, Nanjing, 210042, China.
authors.forename: Heng
authors.initials: H
authors.lastname: Gu
mesh_terms: D001343:Autophagy; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D006367:HeLa Cells; D006801:Humans; D015603:Keratinocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D011887:Raffinose / Q000493:pharmacokinetics*; D015398:Signal Transduction / Q000187:drug effects; D013395:Sucrose / Q000494:pharmacology*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D014199:Trehalose / Q000494:pharmacology*
chemical_list: C477012:MAP1LC3A protein, human; D008869:Microtubule-Associated Proteins; D013395:Sucrose; D014199:Trehalose; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D011887:Raffinose