Anthraquinone-2-sulfonic acid (AQ2S) is a novel neurotherapeutic agent.
Anthraquinone-2-sulfonic acid (AQ2S) is a novel neurotherapeutic agent.
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DOI：
10.1038/cddis.2012.187
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发表时间：
2013-01-10
影响因子：
9
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中科院分区：
文献类型：
--
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蒽醌衍生物如大黄素最近已被证明在β淀粉样蛋白β（Aβ）和tau聚集诱导的细胞死亡模型中具有保护作用。作用机制可能涉及预处理效应、抗聚集特性和/或增强磷脂酰肌醇-3-激酶（PI 3 K）/AKT存活机制。我们研究了几种天然（大黄素，大黄酸和芦荟苷）和合成（AQ 2S）蒽醌，筛选治疗后的治疗效益在两种模型的神经元死亡，即过氧化氢（H2 O2）和星形孢菌素（STS）诱导的损伤。大黄素，大黄酸，芦荟素治疗未能减少过氧化氢损伤。此外，与大黄素表现得像一种轻度毒素一致，它在我们治疗后范式中使用的最高浓度（50 μM）下加剧了氧化损伤，并有效抑制AKT。相比之下，AQ 2S具有神经保护作用。在50和75 μM浓度下，可减少H2 O2损伤。此外，AQ 2S有效地抑制staurosporine（STS）诱导的损伤。其作用机制涉及半胱天冬酶抑制和AKT激活。然而，用LY 294002阻断AKT信号传导未能消除STS测定中AQ 2S介导的保护。这是首次报道AQ 2S是一种新的神经保护化合物和新型半胱天冬酶抑制剂的研究。
Anthraquinone derivatives such as emodin have recently been shown to protect in models of beta amyloid β (Aβ) and tau aggregation-induced cell death. The mechanisms of action possibly involve preconditioning effects, anti-aggregation properties, and/or enhancing the phosphatidylinositol-3-kinase (PI3K)/AKT survival mechanism. We studied several natural (emodin, rhein, and aloin) and synthetic (AQ2S) anthraquinones, to screen for post-treatment therapeutic benefit in two models of neuronal death, namely hydrogen peroxide (H2O2) and staurosporine (STS)-induced injury. Treatment with emodin, rhein, or aloin failed to reduce H2O2 injury. Moreover, consistent with emodin behaving like a mild toxin, it exacerbated oxidative injury at the highest concentration used (50 μM) in our post-treatment paradigm, and potently inhibited AKT. In contrast, AQ2S was neuroprotective. It reduced H2O2 injury at 50 and 75 μM. In addition, AQ2S potently inhibited staurosporine (STS)-induced injury. The mechanisms of action involve caspase inhibition and AKT activation. However, blockade of AKT signaling with LY294002 failed to abolish AQ2S-mediated protection on the STS assay. This is the first study to report that AQ2S is a new neuroprotective compound and a novel caspase inhibitor.
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影响因子：
12.4
作者：
Deshmukh, M;Johnson, EM
通讯作者：
Johnson, EM
影响因子：
2.9
作者：
Colombo, Raffaella;Carofti, Angelo;De Lorenzi, Ersilia
通讯作者：
De Lorenzi, Ersilia
影响因子：
5.3
作者：
Carloni, Silvia;Girelli, Silvia;Balduini, Walter
通讯作者：
Balduini, Walter
影响因子：
8
作者：
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通讯作者：
Caflisch, Amedeo
影响因子：
4.8
作者：
Kang, KH;Lee, KH;Choi, KH
通讯作者：
Choi, KH