title: Protective effects of Ndfip1 on MPP(+)-induced apoptosis in MES23.5 cells and its underlying mechanisms.
abstract: Apoptosis has been implicated as one of the important mechanisms involved in the degeneration of dopaminergic neurons in Parkinson's disease (PD). Increasing evidence suggests that Ndfip1 is a neuroprotective protein, and Ndfip1-mediated protein ubiquitination might be a possible survival strategy in neuronal injury. The aim of the present study is to investigate the neuroprotective effect of Ndfip1 on 1-methyl-4-phenylpyridinium (MPP(+))-treated MES23.5 cells and the underlying mechanisms. Results showed that overexpression of Ndfip1 could significantly attenuate MPP(+)-induced cell loss and nuclear condensation. Further experiments demonstrated that Ndfip1 could increase Bcl-2/Bax ratio, suppress cytochrome c release from the mitochondria to cytoplasm and decrease caspase-3 activation induced by MPP(+). These results suggested that Ndfip1 protected MES23.5 cells against MPP(+) by its anti-apoptotic effect. In addition, we found that Ndfip1 overexpression could decrease the protein level of dopamine transporter (DAT). In parallel, proteasome inhibitor MG132 could markedly reverse Ndfip1-induced degradation of DAT. These data suggest that Ndfip1 exerts its inhibitory effect on DAT by modulating DAT degradation, in which ubiquitin-proteasome system activation might be involved. Collectively, our study indicated that the ability to decrease the DAT of Ndfip1 might be one of the mechanisms underlying its protective effect on MPP(+)-induced cell damage in MES23.5 cells.
authors: Department of Neurosurgery, The Affiliated Hospital of Medical College, Qingdao University, Qingdao 266003, China.
authors: Kai
authors: K
authors: Liu
authors: Department of Physiology, Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders and State Key Disciplines: Physiology, Medical College of Qingdao University, Qingdao 266071, China.
authors: Huamin
authors: H
authors: Xu
authors: Department of Neurosurgery, The Affiliated Hospital of Medical College, Qingdao University, Qingdao 266003, China.
authors: Hengwei
authors: H
authors: Xiang
authors: Department of Neurosurgery, The Affiliated Hospital of Medical College, Qingdao University, Qingdao 266003, China. Electronic address: sunpengqd@163.com.
authors: Peng
authors: P
authors: Sun
authors: Department of Physiology, Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders and State Key Disciplines: Physiology, Medical College of Qingdao University, Qingdao 266071, China. Electronic address: jxiaxie@public.qd.sd.cn.
authors: Junxia
authors: J
authors: Xie
mesh_terms: D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D045304:Cytochromes c / Q000378:metabolism; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006540:Herbicides / Q000633:toxicity*; D006822:Hybrid Cells; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D013997:Time Factors; D014162:Transfection; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D006540:Herbicides; D008565:Membrane Proteins; C451223:NDFIP1 protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D051028:bcl-2-Associated X Protein; D049452:Green Fluorescent Proteins; D045304:Cytochromes c; D053148:Caspase 3; D015655:1-Methyl-4-phenylpyridinium
keywords: Apoptosis; Dopamine transporter; MPP(+); Ndfip1; Parkinson's disease