Tricyclodecan-9-yl-xanthogenate (D609) mechanism of actions: a mini-review of literature.
Tricyclodecan-9-yl-xanthogenate (D609) mechanism of actions: a mini-review of literature.
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DOI：
10.1007/s11064-011-0659-z
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发表时间：
2012-04
影响因子：
4.4
通讯作者：
Gusain, A.
中科院分区：
文献类型：
--
作者：
Adibhatla, Rao Muralikrishna;Hatcher, J. F.;Gusain, A.
关键词：
三环十二烷-9-基黄原酸酯(D609)以其抗病毒和抗肿瘤特性而闻名。D609的作用被广泛归因于抑制磷脂酰胆碱(PC)特异性磷脂酶C(PC-PLC)。D609还抑制鞘磷脂合成酶(SMS)。PC-PLC和/或SMS抑制会影响脂质第二信使1，2-二酰甘油(DAG)和/或神经酰胺。有证据表明，PC-PLC和/或SMS的抑制影响了细胞周期，抑制了细胞的增殖，并促进了体内和体外的研究。黄原酸酯化合物也是有效的抗氧化剂，D609由于其抗氧化特性而减少了Aβ诱导的毒性。锌离子是PC-PLC酶活性所必需的，D609对酶活性的抑制可能是由于其对锌离子的络合作用。D609还被提出用来抑制酸性鞘磷脂酶或下调缺氧诱导因子-1α；然而，这些都是与PC-PLC抑制有关的下游事件。哺乳动物PC-PLC的特征仅限于抑制酶活性(通常以细菌PC-PLC为标准使用Amplex红检测)。哺乳动物的PC-PLC尚未被克隆；没有测序和结构信息。D609在癌症研究中显示出希望，减少动脉粥样硬化斑块(抑制PC-PLC)和中风后脑梗塞(PC-PLC或SMS)。D609作为促炎细胞因子的拮抗剂被认为是PC-PLC的作用。本综述的目的是对文献进行综合评价，并总结其发现及其与细胞周期和中枢神经系统病理的相关性。
Tricyclodecan-9-yl-xanthogenate (D609) is known for its antiviral and antitumor properties. D609 actions are widely attributed to inhibiting phosphatidylcholine (PC)-specific phospholipase C (PC-PLC). D609 also inhibits sphingomyelin synthase (SMS). PC-PLC and/or SMS inhibition will affect lipid second messengers 1,2-diacylglycerol (DAG) and/or ceramide. Evidence indicates either PC-PLC and/or SMS inhibition affected the cell cycle and arrested proliferation, and stimulated differentiation in various in vitro and in vivo studies. Xanthogenate compounds are also potent antioxidants and D609 reduced Aβ-induced toxicity, attributed to its antioxidant properties. Zn2+ is necessary for PC-PLC enzymatic activity; inhibition by D609 might be attributed to its Zn2+ chelation. D609 has also been proposed to inhibit acidic sphingomyelinase or down-regulate hypoxia inducible factor-1α; however these are downstream events related to PC-PLC inhibition. Characterization of the mammalian PC-PLC is limited to inhibition of enzymatic activity (frequently measured using Amplex red assay with bacterial PC-PLC as a standard). The mammalian PC-PLC has not been cloned; sequenced and structural information is unavailable. D609 showed promise in cancer studies, reduced atherosclerotic plaques (inhibition of PC-PLC) and cerebral infarction after stroke (PC-PLC or SMS). D609 actions as an antagonist to pro-inflammatory cytokines have been attributed to PC-PLC. The purpose of this review is to comprehensively evaluate the literature and summarize the findings and relevance to cell cycle and CNS pathologies.
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影响因子：
7.4
作者：
Ansari, Mubeen Ahmad;Joshi, Gururaj;Butterfield, D. Allan
通讯作者：
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DOI：
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发表时间：
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影响因子：
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作者：
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影响因子：
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作者：
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