Zhang Jun-Jing, Zhang Rui-Fang, Meng Xing-Kai
Department of Surgery, The Affiliated Hospital of Inner Mongolia Medical College, 1 Tongdao Beijie, Hohhot, 010050, China.
Neurosci Lett. 2009 Oct 30;464(3):165-9. doi: 10.1016/j.neulet.2009.08.037. Epub 2009 Aug 20.
The neurotoxicity of aggregated beta-amyloid (Abeta) has been implicated as a critical cause in the pathogenesis of Alzheimer's disease (AD). It can cause neurotoxicity in AD by evoking a cascade of oxidative damage-dependent apoptosis to neurons. In the present study, we for the first time investigated the protective effect of pyrroloquinoline quinone (PQQ), an anionic, water soluble compound that acts as a redox cofactor of bacterial dehydrogenases, on Abeta-induced SH-SY5Y cytotoxicity. Abeta(25-35) significantly reduced cell viability, increased the number of apoptotic-like cells, and increased ROS production. All of these phenotypes induced by Abeta(25-35) were markedly reversed by PQQ. PQQ pretreatment recovered cells from Abeta(25-35)-induced cell death, prevented Abeta(25-35)-induced apoptosis, and decreased ROS production. PQQ strikingly decreased Bax/Bcl-2 ratio, and suppressed the cleavage of caspase-3. These results indicated that PQQ could protect SH-SY5Y cells against beta-amyloid induced neurotoxicity.
聚集的β-淀粉样蛋白（Aβ）的神经毒性被认为是阿尔茨海默病（AD）发病机制中的一个关键原因。它可通过引发一系列依赖氧化损伤的神经元凋亡而在AD中导致神经毒性。在本研究中，我们首次研究了吡咯喹啉醌（PQQ）——一种作为细菌脱氢酶氧化还原辅助因子的阴离子水溶性化合物——对Aβ诱导的SH-SY5Y细胞毒性的保护作用。Aβ（25-35）显著降低细胞活力，增加凋亡样细胞数量，并增加活性氧（ROS）生成。PQQ显著逆转了由Aβ（25-35）诱导的所有这些表型。PQQ预处理使细胞从Aβ（25-35）诱导的细胞死亡中恢复，防止Aβ（25-35）诱导的凋亡，并降低ROS生成。PQQ显著降低Bax/Bcl-2比率，并抑制caspase-3的裂解。这些结果表明，PQQ可保护SH-SY5Y细胞免受β-淀粉样蛋白诱导的神经毒性。
