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The Toxicity of a Chemically Synthesized Peptide Derived from Non-Integrin Platelet Collagen Receptors

机译:非整合素血小板胶原受体衍生的化学合成肽的毒性

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A chemically synthesized peptide derived from platelet non-integrin collagen receptor has been shown to be an effective agent for inhibiting collagen-induced platelet aggregation and adhesion of washed radiolabeled platelets onto natural matrices and collagen coated microtiter plates. In order to be a therapeutic agent, we have used a cell culturing system and an animal model to test its cytotoxicities. In cell culture experiments, the peptide is not toxic to MEG-01, a megakaryoblastic cell line. Prior to performing experiments in rats, the existence of both platelet type I and type III collagen receptors and its functional roles in rat platelets had to be established. In this investigation, we report that rat platelets contain both receptors and the cHyB peptide inhibits both type I and type III collagen-induced rat platelet aggregation. In addition, analysis of the rat sera collected at various time intervals following an injection of cHyB into the rat-tail vein, did not show an increase in the activity of key enzymes which indicate tissue and/or organ damage. These results suggest that the cHyB peptide is safe and its development into a potential therapeutic agent for inhibiting thrombi formation is possible.
机译:已显示衍生自血小板非整联蛋白胶原蛋白受体的化学合成肽是抑制胶原蛋白诱导的血小板凝集和将洗涤后的放射性标记的血小板粘附至天然基质和胶原蛋白包被的微量滴定板上的有效试剂。为了成为治疗剂,我们使用了细胞培养系统和动物模型来测试其细胞毒性。在细胞培养实验中,该肽对巨核细胞系MEG-01无毒。在大鼠中进行实验之前,必须确定血小板I型和III型胶原受体的存在及其在大鼠血小板中的功能。在这项研究中,我们报告大鼠血小板包含受体和cHyB肽抑制I型和III型胶原诱导的大鼠血小板聚集。另外,在将cHyB注射入鼠尾静脉后在不同时间间隔收集的鼠血清的分析未显示出指示组织和/或器官损伤的关键酶的活性增加。这些结果表明,cHyB肽是安全的,并且有可能发展成为抑制血栓形成的潜在治疗剂。

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