Daverey Amita, Agrawal Sandeep K
Department of Surgery, Division of Neurosurgery, University of Nebraska Medical Center, Omaha, NE, USA.
Department of Surgery, Division of Neurosurgery, University of Nebraska Medical Center, Omaha, NE, USA.
Neuroscience. 2016 Oct 1;333:92-103. doi: 10.1016/j.neuroscience.2016.07.012. Epub 2016 Jul 14.
Oxidative stress plays a critical role in various neurodegenerative diseases, thus alleviating oxidative stress is a potential strategy for therapeutic intervention and/or prevention of neurodegenerative diseases. In the present study, alleviation of oxidative stress through curcumin is investigated in A172 (human glioblastoma cell line) and HA-sp (human astrocytes cell line derived from the spinal cord) astrocytes. H2O2 was used to induce oxidative stress in astrocytes (A172 and HA-sp). Data show that H2O2 induces activation of astrocytes in dose- and time-dependent manner as evident by increased expression of GFAP in A172 and HA-sp cells after 24 and 12h respectively. An upregulation of Prdx6 was also observed in A172 and HA-sp cells after 24h of H2O2 treatment as compared to untreated control. Our data also showed that curcumin inhibits oxidative stress-induced cytoskeleton disarrangement, and impedes the activation of astrocytes by inhibiting upregulation of GFAP, vimentin and Prdx6. In addition, we observed an inhibition of oxidative stress-induced inflammation, apoptosis and mitochondria fragmentation after curcumin treatment. Therefore, our results suggest that curcumin not only protects astrocytes from H2O2-induced oxidative stress but also reverses the mitochondrial damage and dysfunction induced by oxidative stress. This study also provides evidence for protective role of curcumin on astrocytes by showing its effects on attenuating reactive astrogliosis and inhibiting apoptosis.
氧化应激在多种神经退行性疾病中起关键作用,因此减轻氧化应激是治疗干预和/或预防神经退行性疾病的潜在策略。在本研究中,研究了姜黄素在A172(人胶质母细胞瘤细胞系)和HA-sp(源自脊髓的人星形胶质细胞系)星形胶质细胞中减轻氧化应激的作用。使用过氧化氢(H2O2)诱导星形胶质细胞(A172和HA-sp)产生氧化应激。数据显示,H2O2分别在24小时和12小时后,以剂量和时间依赖性方式诱导A172和HA-sp细胞中胶质纤维酸性蛋白(GFAP)表达增加,从而激活星形胶质细胞。与未处理的对照相比,在H2O2处理24小时后,A172和HA-sp细胞中也观察到过氧化物酶6(Prdx6)上调。我们的数据还表明,姜黄素可抑制氧化应激诱导的细胞骨架紊乱,并通过抑制GFAP、波形蛋白和Prdx6的上调来阻碍星形胶质细胞的激活。此外,我们观察到姜黄素处理后可抑制氧化应激诱导的炎症、凋亡和线粒体碎片化。因此,我们的结果表明,姜黄素不仅能保护星形胶质细胞免受H2O2诱导的氧化应激,还能逆转氧化应激诱导的线粒体损伤和功能障碍。本研究还通过展示姜黄素对减轻反应性星形胶质细胞增生和抑制凋亡的作用,为其对星形胶质细胞的保护作用提供了证据。