title: xCT deficiency induces autophagy via endoplasmic reticulum stress activated p38-mitogen-activated protein kinase and mTOR in sut melanocytes.
abstract: xCT, the functional subunit of the system xc(-) encoded by the Slc7a11 gene, plays an important role in maintaining intracellular glutathione (GSH) levels. In previous study, we have indicated that xCT deficiency induces OS and that OS triggers apoptosis through JNK pathway, however, this induction of apoptotic features did not fully explain the cell death induced by xCT deficiency. In the current study, we demonstrated that sut melanocytes of xCT deficiency showed activation of both ER stress and autophagy. And that the activation of autophagy by xCT deficiency was mediated by ER stress induced activation of p38 MAPK and NF-κB pathways and subsequently inhibited functions of Akt/mTOR/p70S6K survival pathways, ultimately led to autophagic cell death of sut melanocytes. Our novel results provided important insights into understanding the mechanism associated with xCT deficiency.
authors.affiliation: School of biomedical engineering, School of Biomedical Engineering and Technology, Tianjin Medical University, 22 Qixiangtai Road, Tianjin 300070, China.
authors.forename: XueTing
authors.initials: X
authors.lastname: Zheng
authors.affiliation: School of biomedical engineering, School of Biomedical Engineering and Technology, Tianjin Medical University, 22 Qixiangtai Road, Tianjin 300070, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.affiliation: School of biomedical engineering, School of Biomedical Engineering and Technology, Tianjin Medical University, 22 Qixiangtai Road, Tianjin 300070, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhao
authors.affiliation: School of biomedical engineering, School of Biomedical Engineering and Technology, Tianjin Medical University, 22 Qixiangtai Road, Tianjin 300070, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Yan
authors.affiliation: School of biomedical engineering, School of Biomedical Engineering and Technology, Tianjin Medical University, 22 Qixiangtai Road, Tianjin 300070, China.
authors.forename: YiXuan
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Department of Rehabilitation and sports medicine, Tianjin Medical University, 22 Qixiangtai Road, Tianjin 300070, China. Electronic address: zhaolp_2004@163.com.
authors.forename: LiPing
authors.initials: L
authors.lastname: Zhao
authors.affiliation: School of biomedical engineering, School of Biomedical Engineering and Technology, Tianjin Medical University, 22 Qixiangtai Road, Tianjin 300070, China. Electronic address: qiaohaixuan@aliyun.com.
authors.forename: Haixuan
authors.initials: H
authors.lastname: Qiao
mesh_terms: D027182:Amino Acid Transport System y+ / Q000172:deficiency* / Q000378:metabolism; D000818:Animals; D001343:Autophagy / Q000502:physiology*; D059865:Endoplasmic Reticulum Stress / Q000502:physiology*; D020935:MAP Kinase Signaling System; D008544:Melanocytes / Q000166:cytology* / Q000378:metabolism*; D051379:Mice; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D027182:Amino Acid Transport System y+; C492255:Slc7a11 protein, mouse; C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Autophagy; ER stress; Sut melanocytes; xCT