NCAM-140 Translocation into Lipid Rafts Mediates the Neuroprotective Effects of GDNF
NCAM-140 Translocation into Lipid Rafts Mediates the Neuroprotective Effects of GDNF
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DOI：
10.1007/s12035-016-9749-x
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
高殿帅
中科院分区：
文献类型：
--
作者：
李俐;陈慧珍;王萌;陈芳芳;高锦;孙申;李云庆;高殿帅
Abstract Glial cell line-derived neurotrophic factor.(GDNF) is a potent neurotrophic factor for substantia.nigra dopaminergic (DA) neuronal cells. Recent studies.have demonstrated that neural cell adhesion molecule.functions as a signal transduction receptor for GDNF..The purpose of this study is to reveal whether neural cell.adhesion molecule (NCAM) mediates the protective effects.of GDNF on DA neuronal cells and further explore.the mechanisms involved. We utilized SH-SY5Y cell line.to establish a model of 6-hydroxydopamine (6-OHDA)-.injured DA neuronal cells. Lentiviral vectors were constructed.to knockdown or overexpress NCAM-140, and.a density gradient centrifugation method was employed.to separate membrane lipid rafts. 3-(4,5-Dimethythiazol-.2-yl)-2,5-diphenyl tetrazolium bromide (MTT), flow cytometric.analysis, and western blotting were used to evaluate.the protective effects of GDNF. The results showed.that GDNF could protect 6-OHDA-injured SH-SY5Y.cells via improving cell viability and decreasing the cell.death rate and cleaved caspase-3 expression. NCAM-140.knockdown decreased cell viability and increased the cell.death rate and cleaved caspase-3 expression, while its.overexpression had the opposite effects. Notably, the.amount of NCAM-140 located in lipid rafts increased after.GDNF treatment. Pretreatment with 2-bromopalmitate,.a specific inhibitor of protein palmitoylation, suppressed.NCAM-140 translocation to lipid rafts and reduced the.NCAM-mediated protective effects of GDNF on injured.DA neuronal cells. Our results suggest that GDNF have.the protective effects on injured DA cells by influencing.NCAM-140 translocation into lipid rafts.
