期刊
NEUROCHEMICAL RESEARCH
卷 37, 期 4, 页码 671-679出版社
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s11064-011-0659-z
关键词
Antioxidant; Cell cycle; Ceramide; Cytokines; Glutathione; Inflammation; Microglia/macrophage; Phosphatidylcholine; Phospholipase C; PC-PLC; Proliferation; Reactive oxygen species; Sphingomyelin synthase; Stroke
资金
- NIH [R01 NS063959]
- AHA [11GRNT7360066]
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 A beta-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-1 alpha; however these are down-stream 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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