Preso在PC12细胞氧化应激损伤中的作用

Effects of Preso on oxidative stress injury in PC12 cells

目的通过建立大鼠肾上腺髓质嗜铬瘤分化细胞株(PC12)氧化应激损伤模型,研究一类新型结构蛋白脊椎形态发生突触后致密物质95(PSD-95)相关调节因子(Preso)在氧化应激损伤中的作用以及有可能的作用方式。方法建立PC12细胞氧化应激损伤模型,通过Western blot法检测损伤后Preso蛋白表达变化;通过干涉Preso蛋白表达,四甲基啖唑蓝(MTT)检测细胞存活率及乳酸脱氢酶(LDH)检测细胞损伤程度评价Preso在氧化应激损伤中的作用;使用地佐环平(MK-801)阻断离子型谷氨酸受体(NMDAR)激活,然后通过MTT法检测细胞存活率及LDH法检测细胞损伤程度,分析Preso在氧化应激损伤中可能起作用的途径。结果氧化应激损伤能够使Preso蛋白表达增高,而干涉Preso蛋白表达能够有效提高氧化应激损伤后细胞存活率,而抑制NMDAR激活会削弱干涉Preso蛋白表达的细胞保护作用。结论 Preso对于氧化应激损伤起到了促进的作用,干涉Preso表达可减轻细胞氧化应激损伤;Preso蛋白很可能通过结合突触后致密物质95进而促进NMDA受体激活,起到加重细胞氧化应激损伤作用。

Objective The effects of a novel scaffold protein postsynaptic density-95 （PSD-95）-interacting regulator of spine morphogenesis （Preso） on oxidative stress injury and the related molecular pathway are investigated. Methods After establishing the oxidative stress injury model in PC12 cells, the changes of Preso expression were measured by Western blot analysis. After interfering the expression of Preso, 3-（4,5-dimethyl-2- thiazolyl）-2,5-diphenyl-2-H-tetrazolium bromide （MTT） and lactate dehydrogenase （LDH） analysis were used to evaluate the role of Preso on oxidative stress injury through evaluating cell injury. Furthermore, N-methyl-D-aspartate receptor （NMDAR） activation was blocked by dizocilpine （MK-801） to analyze the possible molecular pathway. Results Oxidative stress injury increased the expression of Preso; down-regulation of Preso expression improved effectively the cell viability against oxidative stress; MK-801 lowered the cell viability by interfering the expression of Preso. Conclusion Preso promotes the oxidative stress injury. Interfering of the expression of Preso improves the cell viability against oxidative stress. The Preso protein is likely to aggravate oxidative injury by promoting the activation of NMDAR through bind PSD-95.