title: Inhibition of Aβ(25-35)-induced cell apoptosis by low-power-laser-irradiation (LPLI) through promoting Akt-dependent YAP cytoplasmic translocation.
abstract: Deposition of amyloid-β-peptide (Aβ) in the brain is considered a pathological hallmark of Alzheimer's disease (AD). Our previous studies show that Yes-associated protein (YAP) is involved in the regulation of apoptosis induced by Aβ(25-35) through YAP nuclear translocation and its pro-apoptotic function is mediated by its interaction with p73. In the present study, we first found that Low-power laser irradiation (LPLI) promoted YAP cytoplasmic translocation and inhibited Aβ(25-35)-induced YAP nuclear translocation. Moreover, the cytoplasmic translocation was in an Akt-dependent manner. Activated Akt by LPLI phosphorylated YAP on ser127 (S127) and resulted in decreasing the interaction between YAP and p73, and in suppressing the proapoptotic gene bax expression following Aβ(25-35) treatment. Inhibition of Akt expression by siRNA significantly abolished the effect of LPLI. More importantly, LPLI could inhibit Aβ(25-35)-induced cell apoptosis through activation of Akt/YAP/p73 signaling pathway. Therefore, our findings first suggest that YAP may be a therapeutic target and these results directly point to a potential therapeutic strategy for the treatment of AD through Akt/YAP/p73 signaling pathway with LPLI.
authors.affiliation: MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou, China.
authors.forename: Heng
authors.initials: H
authors.lastname: Zhang
authors.forename: Shengnan
authors.initials: S
authors.lastname: Wu
authors.forename: Da
authors.initials: D
authors.lastname: Xing
mesh_terms: D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors*; D000818:Animals; D017209:Apoptosis / Q000528:radiation effects*; D018797:Cell Cycle Proteins; D002467:Cell Nucleus / Q000378:metabolism; D002470:Cell Survival; D004268:DNA-Binding Proteins / Q000378:metabolism; D004789:Enzyme Activation; D015870:Gene Expression; D057809:HEK293 Cells; D006801:Humans; D047468:Immunoprecipitation; D028022:Low-Level Light Therapy; D009687:Nuclear Proteins / Q000378:metabolism*; D016716:PC12 Cells; D010446:Peptide Fragments / Q000037:antagonists & inhibitors*; D010766:Phosphorylation; D011485:Protein Binding; D021381:Protein Transport / Q000528:radiation effects*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism*; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; C494826:BAX protein, human; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D010446:Peptide Fragments; C000606460:TP73 protein, human; D014157:Transcription Factors; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins; C456659:YY1AP1 protein, human; C074636:amyloid beta-protein (25-35); D051028:bcl-2-Associated X Protein; D051057:Proto-Oncogene Proteins c-akt