Yazdanparast Razieh, Shaykhalishahi Hamed
Institute of Biochemistry and Biophysics, University of Tehran, P.O. Box 13145-1384, Tehran, Iran.
Toxicol In Vitro. 2009 Oct;23(7):1277-83. doi: 10.1016/j.tiv.2009.07.024. Epub 2009 Jul 22.
The role of beta-amyloid (A beta) in the pathogenesis of Alzheimer's disease (AD) is frequently reported in the literature. Though the exact mode of action is not known, it is suggested that A beta induces cell death through induction of oxidative stress possibly through hydrogen peroxide generation. In that case, antioxidants should be capable of attenuating the A beta-induced cytotoxicities. In that regard, we evaluated the effect(s) of a triazine-derivative, AA3E2, with established antioxidant activity. Pretreatment of SK-N-MC neuroblastoma cells with AA3E2, followed by exposure to A beta(1-42) showed 28.3% higher viability relative to the control cells which has not been treated with AA3E2. In addition, AA3E2 inhibited caspase-3 activation caused by A beta(1-42) and it attenuated A beta(1-42)-induced intracellular ROS (reactive oxygen species) accumulation. The lower level of intracellular free radicals was further confirmed by higher and lower activities of intracellular catalase and superoxide dismutase, respectively. These observations, parallel to the literature data, reconfirm the oxidative stress disrupting role of A beta(1-42) peptide. Thus, sequestration of this role by potential antioxidants such as AA3E2 might happen to be a suitable strategy for future treatments of AD.
β-淀粉样蛋白（Aβ）在阿尔茨海默病（AD）发病机制中的作用在文献中经常被报道。尽管确切的作用方式尚不清楚，但有人提出Aβ可能通过产生过氧化氢诱导氧化应激从而导致细胞死亡。在这种情况下，抗氧化剂应该能够减轻Aβ诱导的细胞毒性。在这方面，我们评估了一种具有既定抗氧化活性的三嗪衍生物AA3E2的作用。用AA3E2预处理SK-N-MC神经母细胞瘤细胞，然后暴露于Aβ（1-42），结果显示其存活率比未用AA3E2处理的对照细胞高28.3%。此外，AA3E2抑制了Aβ（1-42）引起的半胱天冬酶-3激活，并减轻了Aβ（1-42）诱导的细胞内活性氧（ROS）积累。细胞内过氧化氢酶和超氧化物歧化酶活性分别升高和降低，进一步证实了细胞内自由基水平较低。这些观察结果与文献数据一致，再次证实了Aβ（1-42）肽的氧化应激破坏作用。因此，用潜在的抗氧化剂如AA3E2来消除这种作用可能是未来治疗AD的合适策略。
