Oxidative Stress Induces Neuronal Apoptosis Through Suppressing Transcription Factor EB Phosphorylation at Ser467
文献类型:期刊论文
作者 | Su, Qian2; Zheng, Bin2; Zhang, Xin-hua2; Ma, Dong2; Sun, Yan2; Yang, Zhan2; Wen, Jin-kun2; Wang, Chen-yao1; Yang, Yun-zhi1; Luo, Wen-wen1 |
刊名 | CELLULAR PHYSIOLOGY AND BIOCHEMISTRY |
出版日期 | 2018 |
卷号 | 46期号:4页码:1536-1554 |
ISSN号 | 1015-8987 |
关键词 | Tfeb Akt signalling Phosphorylation Oxidative stress SH-SY5Y cell Neuronal apoptosis |
DOI | 10.1159/000489198 |
文献子类 | Article |
英文摘要 | Background/Aims: This study determined the role and mechanism of action of transcription factor EB (TFEB) in H2O2-induced neuronal apoptosis. Methods: SH-SY5Y cells were treated with Akt inhibitor/activator and different concentrations of H2O2. Cell apoptosis was detected by flow cytometric analysis. Akt and TFEB phosphorylation and PARP cleavage were determined by Western blotting. HEK293T cells were transfected with different truncated TFEB mutants and HA-Akt-WT; SH-SY5Y cells were transfected with Flag-vector, Flag-TFEB, Flag-TFEB-S467A or Flag-TFEB-S467D; and TFEB interaction with Akt was determined by co-immunoprecipitation and GST pull-down assays. Results: A low concentration of H2O2 induces TFEB phosphorylation at Ser467 and nuclear translocation, facilitating neuronal survival, whereas a high concentration of H2O2 promotes SH-SY5Y cell apoptosis via suppressing TFEB Ser467 phosphorylation and nuclear translocation. The TFEB-S467D mutant is more easily translocated into the nucleus than the non-phosphorylated TFEB-S467A mutant. Further, Akt physically binds to TFEB via its C-terminal tail interaction with the HLH domain of TFEB and phosphorylates TFEB at Ser467. Mutation of TFEB-Ser467 can prevent the phosphorylation of TFEB by Akt, preventing inhibition of oxidative stress-induced apoptosis. Conclusions: Oxidative stress induces neuronal apoptosis through suppressing TFEB phosphorylation at Ser467 by Akt, providing a novel therapeutic strategy for neurodegenerative diseases. (C) 2018 The Author(s) Published by S. Karger AG, Basel |
学科主题 | Cell Biology ; Physiology |
WOS关键词 | KAPPA-B KINASE ; CELL-DEATH ; PARKINSONS-DISEASE ; LYSOSOMAL BIOGENESIS ; AKT PHOSPHORYLATION ; STORAGE DISEASES ; TFEB ; AUTOPHAGY ; ACTIVATION ; PATHWAY |
语种 | 英语 |
出版者 | KARGER |
WOS记录号 | WOS:000433152000018 |
版本 | 出版稿 |
源URL | [http://202.127.25.144/handle/331004/692] |
专题 | 中国科学院上海生命科学研究院营养科学研究所 |
作者单位 | 1.Chinese Acad Sci, Univ Chinese Acad Sci, Shanghai Inst Biol Sci, Key Lab Nutr & Metab,Inst Nutr Sci, Shanghai, Peoples R China, 2.Hebei Med Univ, Dept Biochem & Mol Biol, Key Lab Neural & Vasc Biol, Minist Educ, Shijiazhuang, Hebei, Peoples R China; |
推荐引用方式 GB/T 7714 | Su, Qian,Zheng, Bin,Zhang, Xin-hua,et al. Oxidative Stress Induces Neuronal Apoptosis Through Suppressing Transcription Factor EB Phosphorylation at Ser467[J]. CELLULAR PHYSIOLOGY AND BIOCHEMISTRY,2018,46(4):1536-1554. |
APA | Su, Qian.,Zheng, Bin.,Zhang, Xin-hua.,Ma, Dong.,Sun, Yan.,...&,.(2018).Oxidative Stress Induces Neuronal Apoptosis Through Suppressing Transcription Factor EB Phosphorylation at Ser467.CELLULAR PHYSIOLOGY AND BIOCHEMISTRY,46(4),1536-1554. |
MLA | Su, Qian,et al."Oxidative Stress Induces Neuronal Apoptosis Through Suppressing Transcription Factor EB Phosphorylation at Ser467".CELLULAR PHYSIOLOGY AND BIOCHEMISTRY 46.4(2018):1536-1554. |
入库方式: OAI收割
来源:上海营养与健康研究所
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