目的 探讨五味子酚 (schisanhenol,Sal) 对H2O2诱导人神经母细胞瘤(SH-SY5Y)细胞的保护作用及可能机制。方法 SH-SY5Y 细胞给予Sal (1,10和50 μmol·L-1 ) 处理4 h 后给予H2O2 100 μmol·L-1 处理 24 h,利用MTT 法测定Sal对H2O2损伤的 SH-SY5Y 细胞存活率的影响,Western blot 检测Sal对H2O2诱导的 SH-SY5Y 细胞中沉默信息调节因子1(silent information regulator 1,SIRT1)、PGC-1α、p-tau(S396) 蛋白的表达。结果 Sal可明显提高H2O2损伤的 SH-SY5Y 细胞的生存率,Western blot 检测结果显示,H2O2处理后p-tau(S396) 位点 tau 蛋白含量增加,SIRT1和PGC-1α的表达下降。Sal能够增加SIRT1和PGC-1α的表达,降低 p-tau 含量。结论 Sal对H2O2损伤的 SH-SY5Y 细胞具有一定保护作用,并可能通过上调SIRT1蛋白的表达、降低tau 蛋白的磷酸化发挥神经保护作用。
Abstract
OBJECTIVE To investigate the protective effect and possible mechanism of schisanhenol(Sal) in SH-SY5Y cell induced by H2O2. METHODS SH-SY5Y cells were treated with Sal (1,10 and 50 μmol·L-1) for 4 h and then exposed to H2O2 100 μmol·L-1 for 24 h. Cell viability was measured by MTT assay. The expressions of silent information regulator 1(SIRT1), PGC-1α and p-tau (S396) protein were detected using Western blotting. RESULTS MTT results showed that Sal significantly increased the survival rate of SH-SY5Y cell damaged by H2O2. Western blotting analysis showed that H2O2 reduced the expressions of SIRT1 and PGC-1α in SH-SY5Y cells. However, tau protein content was increased by H2O2 at p-tau(S396) sites. Sal treatment significantly increased the levels of SIRT1 and PGC-1α and decreased p-tau(S396) level induced by H2O2 in SH-SY5Y cells. CONCLUSION These results suggest that Sal has a protective effect on H2O2 damaged SH-SY5Y cells, which is related to up regulating the expressions of SIRT1 and PGC-1α protein and decreasing the phosphorylation of tau protein.
关键词
五味子酚 /
过氧化氢 /
沉默信息调节因子1 /
人神经母细胞瘤 /
tau 蛋白
{{custom_keyword}} /
Key words
schisanhenol /
hydrogen peroxide /
silent information regulator 1 /
SH-SY5Y /
tau protein
{{custom_keyword}} /
中图分类号：
R965
{{custom_clc.code}}
({{custom_clc.text}})
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
[1] FEDERICO A, CARDAIOLI E, DA POZZO P, et al. Mitochondria, oxidative stress and neurodegeneration [J]. J Neurol Sci, 2012, 322(1-2): 254-262.
[2] SULTANA R, BUTTERFIELD D A. Oxidative modification of brain proteins in Alzheimer′s disease: perspective on future studies based on results of redox proteomics studies [J]. J Alzheimers Dis, 2013, 33(suppl 1): 243-251.
[3] ZHOU S Y, DENG Z R, TAN L, et al. Protection effect of schisanhenol on learning and memory acquired disorder induced by scopolamine in mice[J]. Chin Pham J(中国药学杂志), 2014, 49(23): 63-67.
[4] ALBANI D, POLITO L, FORLONI G. Sirtuins as novel targets for Alzheimer′s disease and other neurodegenerative disorders: experimental and genetic evidence [J]. J Alzheimers Dis, 2010, 19(1): 11-26.
[5] YANG X R, WANG R, QIN H P. Neuroprotective role of silent information regulator 1 in Alzheimer′s disease [J]. Acta Physiol Sin(生理学报), 2011, 63(4): 396-400.
[6] LI F, ZHAO Y. PGC-1α and neurodegenerative diseases[J]. J Brain Nerv Dis(脑与神经疾病杂志), 2012, 20(6): 466-468.
[7] RODGERS J T, LERIN C, GERHART H Z, et al. Metabolic adaptations through the PGC-1α and SIRT1 pathways [J]. FEBS Lett, 2008, 582(1): 46-53.
[8] RASOURI S, LAGOUGE M, AUWERX J, et al. SIRT1/PGC-1: a neuroprotective axis? [J]. Med Sci (Paris), 2007, 23(10): 840-844.
[9] WANG R, LI J J, DIAO S, et al. Metabolic stress modulates Alzheimer′s β-secretase gene transcription via SIRT1-PPARγ-PGC-1 in neurons [J]. Cell Metab, 2013, 17(5): 685-694.
[10] LI L. Protective effects of schisanhenol, salvianolic acid A and SY-L on oxidative stress induced injuries of cerebral cells and their mechanisms [J]. Prog Physiol Sci(生理科学进展), 1998, 22(1): 35-38.
[11] LI L, LIU G T. Protective effects of schisanhenol and salvianolic acid a in apoptosis of rat cerebral cells induced by H2O2 [J]. Chin J Pharmacol Toxicol (中国药理学与毒理学杂志), 1996, 10(2): 92.
[12] YU L H, LIU G T. Schisanhenol attenuated ox-LDL-induced apoptosis and reactive oxygen species generation in bovine aorta endothelial cells in vitro [J]. Asian Nat Prod Res(亚洲天然产物研究), 2008, 10(7-8): 799-806.
[13] FENG Y, XIA Y, YU G, et al. Cleavage of GSK-3β by calpain counteracts the inhibitory effect of Ser9 phosphorylation on GSK-3β activity induced by H2O2[J]. J Neurochem, 2013, 126(2): 234-242.
[14] JULIEN C, TREMBLAY C, EMOND V, et al. Sirtuin 1 reduction parallels the accumulation of tau in Alzheimer disease [J]. J Neuropathol Exp Neurol, 2009, 68(1): 48-58.
[15] MIN S W, CHO S H, ZHOU Y, et al. Acetylation of tau inhibits its degradation and contributes to tauopathy [J]. Neuron, 2010, 67(6): 953-966.
[16] LEE H R, SHIN H K, PARK S Y, et al. Attenuation of β-amyloid-induced tauopathy via activation of CK2α/SIRT1: targeting for cilostazol [J]. J Neurosci Res, 2014, 92(2): 206-217.
[17] YAO E S, TANG Y, LIU X H, et al. TPPU protects tau from H2O2-induced hyperphosphorylation in HEK293/tau cells by regulating PI3K/AKT/GSK-3β pathway [J]. J Huazhong Univ Sci Technol Med Sci(华中科技大学学报:医学版), 2016, 36(6): 785-790.
{{custom_fnGroup.title_cn}}
脚注
{{custom_fn.content}}
基金
齐齐哈尔市科学技术局社会发展攻关项目资助(SFZD-2014023);齐齐哈尔医学院院内科研基金资助项目(QY2013B-01)
{{custom_fund}}
PDF(1750 KB)
