Molecular Mechanism Of TCTP-mediated Apoptosis Induced By High Fat In Islet ? Cells

Objective: This study is to explore the variation of translational controlled tumor protein(TCTP)expression and its effect on islet ? cell proliferation and apoptosis.Combined with experimental data from high-fat fed mouses,we try to reveal the molecular mechanism of high fat induced islet ? cell apoptosis and related signal transduction pathway beyond.Methods: mimicing the effect of fatty acid on ? cell in vivo by culturing islet ? cell with palmitate(PA);analyzing body weight and blood glucose level of high fat fed mouses and their variation with time;exploring protein function through chemical inhibitors and adenovirus mediated target genes transfection;calculating cell viability by MTS;detecting the expression and distribution of proteins and cell apoptosis with immunofluorescence;examining protein activity and expression under different conditions with western blot;checking protein distribution on plasma membrane after membrane protein extraction;verifying purified proteins by mass spectrum.Results: The distribution of CD36 on plasma membrane of INS1 E cells increased after PA treatment,which could mediated fatty acid uptake.The expression level of TCTP decreased in islet ? cells of high fat fed mouses and in PA treated INS1 E cells.TCTP related closely to islet ? cell function and mediated PA-induced cell apoptosis.PA treatment could reduce TCTP expression level via CD36-Fyn-LKB1-AMPK signal transduction pathway,furthermore,lower TCTP expression led to cell apoptosis.The degradation of TCTP might be caused by its ubiquitination.