Abstract:
Oxidative stress-induced neuronal cell loss is considered to be the major mechanism underlying the pathogenesis of neurodegenerative diseases, which could be induced by a high concentration of glutamate. In this study, sargachromenol (SC) was isolated from a marine brown seaweed Sargassum horneri (S. horneri) and its neuroprotective effects against glutamate-induced oxidative stress in HT22 cells were investigated. An MTT assay was applied to assess the cytotoxicity of the SC, and the efficacies of SC were determined by flow cytometry, an analysis of ROS production, quantitative Real-Time PCR, and the Western blot assay. Our results showed that the pretreatment of SC reduced glutamate-induced apoptosis in HT22 cells via inhibiting the sub-G1 population, DNA fragmentation, and nuclear condensation, as well as up-regulating anti-apoptotic protein (Bcl-2) and down-regulating apoptotic proteins (Bax, p53, cleaved-PARP, caspase-3, caspase-9, and cytochrome c). Additionally, SC attenuated glutamate-induced oxidative stress by suppressing mitogen-activated protein kinases (MAPKs;ERK, JNK, and p38) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling (IκBα and NF-κB p65), while activating nuclear factor erythroid-2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) signaling (Nrf2; HO-1, and NQO-1). Our results suggest that SC could be used as a pharmacological candidate for the prevention and treatment of neurodegenerative diseases.
摘要:
氧化应激诱导的神经细胞丢失被认为是神经退行性疾病发病的主要机制。这可能是由高浓度的谷氨酸引起的。在这项研究中,sargachromenol(SC)从海洋棕色海藻Sargassumhorneri(S.horneri)及其对HT22细胞中谷氨酸诱导的氧化应激的神经保护作用。MTT测定法用于评估SC的细胞毒性,通过流式细胞术确定SC的功效,对ROS生产的分析,实时定量PCR,和蛋白质印迹分析。我们的结果表明,SC的预处理通过抑制亚G1群体减少了谷氨酸诱导的HT22细胞凋亡,DNA片段化,和核缩合,以及上调抗凋亡蛋白(Bcl-2)和下调凋亡蛋白(Bax,p53,裂解的PARP,caspase-3,caspase-9和细胞色素c)。此外,SC通过抑制丝裂原激活的蛋白激酶(MAPKs;ERK,JNK,和p38)和活化B细胞的核因子κ轻链增强子(NF-κB)信号(IκBα和NF-κBp65),同时激活核因子红细胞相关因子2(Nrf2)/血红素加氧酶1(HO-1)信号(Nrf2;HO-1和NQO-1)。我们的结果表明,SC可以用作预防和治疗神经退行性疾病的药理候选药物。