用系统生物学方法研究产气荚膜梭菌磷脂酶C诱导细胞内钙瞬变的控制靶点

L. Brenes-Guillén, Man-Sai Acón-Chan, R. Mora-Rodríguez, Laura Monturiol-Gross
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引用次数: 1

摘要

产气荚膜梭菌磷脂酶C (CpPLC)在气性坏疽的发病机制中起关键作用,气性坏疽是一种危及生命的急性感染。CpPLC导致第二信使(如钙)不受调节的产生,并激活PKC、MEK和NFkB等重要信号通路,诱导ROS的产生,从而导致细胞损伤。我们提出了一种系统生物学方法来鉴定潜在的microrna,这些microrna可以作为工具来探索钙通道在CpPLC作用机制中的作用,并最终作为治疗药物,使细胞对这种毒素不那么敏感。结果表明,miR19B1和miR449B是可能影响钙转运相关基因表达的有趣的候选靶点。这种方法可能有助于阐明钙分子相互作用参与CpPLC的作用机制。
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A Systems Biology Approach to Investigate Control Targets of Intracellular Calcium Transients Induced by Clostridium Perfringens Phospholipase C
Clostridium perfringens phospholipase C (CpPLC) plays a key role in the pathogenesis of gas gangrene, an acute and life-threatening infection in humans. CpPLC leads to the unregulated production of second messengers, such as calcium, and activates important signaling pathways like PKC, MEK, and NFkB, inducing ROS production, that leads towards cellular damage. We propose a systems biology approach to identify potential microRNAs which could be used as tools to explore the role of calcium channels in the mechanism of action of CpPLC, and eventually as therapeutic agents that render cells less sensitive to this toxin. Results show that miR19B1 and miR449B are interesting candidate targets which perturbations may affect the expression of genes involved in calcium transport. This approach may be useful to elucidate calcium molecular interactions involved in the CpPLC mechanism of action.
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