title: Impact on Autophagy and Ultraviolet B Induced Responses of Treatment with the MTOR Inhibitors Rapamycin, Everolimus, Torin 1, and pp242 in Human Keratinocytes.
abstract: The mechanistic target of Rapamycin (MTOR) protein is a crucial signaling regulator in mammalian cells that is extensively involved in cellular biology. The function of MTOR signaling in keratinocytes remains unclear. In this study, we detected the MTOR signaling and autophagy response in the human keratinocyte cell line HaCaT and human epidermal keratinocytes treated with MTOR inhibitors. Moreover, we detected the impact of MTOR inhibitors on keratinocytes exposed to the common carcinogenic stressors ultraviolet B (UVB) and UVA radiation. As a result, keratinocytes were sensitive to the MTOR inhibitors Rapamycin, everolimus, Torin 1, and pp242, but the regulation of MTOR downstream signaling was distinct. Next, autophagy induction only was observed in HaCaT cells treated with Rapamycin. Furthermore, we found that MTOR signaling was insensitive to UVB but sensitive to UVA radiation. UVB treatment also had no impact on the inhibition of MTOR signaling by MTOR inhibitors. Finally, MTOR inhibition by Rapamycin, everolimus, or pp242 did not affect the series of biological events in keratinocytes exposed to UVB, including the downregulation of BiP and PERK, activation of Histone H2A and JNK, and cleavage of caspase-3 and PARP. Our study demonstrated that MTOR inhibition in keratinocytes cannot always induce autophagy, and the MTOR pathway does not play a central role in the UVB triggered cellular response.
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, 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, 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, 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, China.
authors.forename: Mengli
authors.initials: M
authors.lastname: Zhang
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, China.
authors.forename: Mei
authors.identifier: 0000-0002-6053-7497
authors.initials: M
authors.lastname: Ju
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, China.
authors.forename: Xu
authors.identifier: 0000-0003-4303-8116
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, China.
authors.forename: Heng
authors.identifier: 0000-0002-3282-1626
authors.initials: H
authors.lastname: Gu
mesh_terms: D001343:Autophagy / Q000187:drug effects* / Q000528:radiation effects; D001798:Blood Proteins / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects / Q000528:radiation effects; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D015536:Down-Regulation / Q000187:drug effects / Q000528:radiation effects; D000091342:Endoplasmic Reticulum Chaperone BiP; D000068338:Everolimus / Q000494:pharmacology*; D006360:Heat-Shock Proteins / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011687:Purines / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects / Q000528:radiation effects; D020123:Sirolimus / Q000494:pharmacology*; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014466:Ultraviolet Rays; D019892:eIF-2 Kinase / Q000378:metabolism
chemical_list: D001798:Blood Proteins; D053148:Caspase 3; D000091342:Endoplasmic Reticulum Chaperone BiP; D000068338:Everolimus; D006360:Heat-Shock Proteins; D006657:Histones; D007211:Indoles; D011065:Poly(ADP-ribose) Polymerases; D011687:Purines; D020123:Sirolimus; D058570:TOR Serine-Threonine Kinases; D019892:eIF-2 Kinase; C031024:torin; C572919:PP242