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路的节点。mTOR 在进化上高度保守,酵母菌和人源mTOR 有高度同源性。在增殖和分化的 PC12 细胞中发现,mTOR抑制延伸因子21A ( elongation facmTOR21A, eEF1A21) 信使核糖核 140 酸(mRNA)向多聚核糖体的募集,调控细胞的增殖[8]。mTOR 不仅可以调控细胞的增殖、存活 等,还广泛参与膜转运、蛋白降解,特别是对蛋白翻译水平的调控。另一个雷帕霉素的下游作 用靶点是空泡膜蛋白1 ( the Vacuole Membrane Protein 1, VMP1) ,后者可募集微管相关蛋白1 轻链3,启动自噬[9]。本研究中，雷帕霉素组与损伤组比较LC3Ⅱ/ LC3Ⅰ的表达明显增多（ P ＜0.05 ），说明脊髓损伤前4 小时腹腔注射Rapamycin 可以促进自噬相关蛋白LC3Ⅱ的表 145 达，证明Rapamycin 可以促进自噬的发生。下一步的研究拟通过给予自噬抑制剂及激活剂干 预，揭示脊髓损伤后自噬的激活对神经修复的作用及分子机制，为脊髓损伤的药物治疗提供 新的方向和靶点。 [参考文献] (References) 150 [1] Xie Z, Klionsky DJ. Autophagosome formation: core machinery and adaptations [ J ]. Nat Cell Biol. 2007. 9(10): 1102-9. [2] Diskin T, Tal-Or P, Erlich S, et al.. Closed head injury induces upregulation of Beclin 1 at the cortical site of injury [ J ]. Neurotrauma. 2005. 22(7): 750-62. [3] Nemoto T, Tanida I, Tanida-Miyake E, et al.. The mouse APG10 homologue, an E2-like enzyme for Apg12p 155 conjugation, facilitates MAP-LC3 modification [ J ]. J Biol Chem. 2003. 278(41): 39517-26. [4] Rubinsztein DC, Gestwicki JE, Murphy LO, Klionsky DJ. Potential therapeutic applications of autophagy [ J ]. Nat Rev Drug Discov. 2007. 6(4): 304-12. [5] Mizushima N, Levine B, Cuervo AM, Klionsky DJ. Autophagy fights disease through cellular self-digestion [ J ]. Nature. 2008. 451(7182): 1069-75. 160 [6] Reggiori F, Klionsky DJ. Autophagosomes: biogenesis from scratch [ J ]. Curr Opin Cell Biol. 2005. 17(4): 415-22. [7] Kanno H, Ozawa H, Sekiguchi A, Itoi E. The role of autophagy in spinal cord injury. Autophagy [ J ]. 2009. 5(3): 390-2. [8] Cavallini G, Donati A, TaddeiM, et al. Evidence for selective mitochondrial autophagy and failure in aging 165 [ J ].Autophagy, 2007, 3 (1) : 26 - 27. [9] RoPolo A, Grasso D, Pardo R, et al. The pancreatitis induced vacuole membrane protein 1 triggers autophagy in ammalian cells [ J ]. J Biol Chem, 2007, 282 ( 51 ) :37124 - 37133. 原创学术论文网Tag：代写论文 代发论文 代写代发论文 代写职称论文 |
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