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植物利钠肽诱导大鼠心肌细胞凋亡。

Induction of apoptosis by plant natriuretic peptides in rat cardiomyoblasts.

机构信息

Medicinal Chemistry and Drug Action, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, VIC 3052, Australia.

出版信息

Peptides. 2010 Jun;31(6):1213-8. doi: 10.1016/j.peptides.2010.03.011. Epub 2010 Mar 20.

Abstract

Atrial natriuretic peptide (ANP) has an important role in maintaining the homeostasis of body fluids and blood pressure and also in preventing cardiac hypertrophy and initiating the process of apoptosis. An immunoreactive analog of ANP was discovered in plants over a decade ago and termed plant natriuretic peptide (PNP). PNP is a small protein that contains sequence and structural similarity to ANP within a predicted protruding psi (psi) loop. Since application of ANP or PNP stimulates similar functional effects in plants, it is conceivable that PNP may have effects on mammalian cells. In this report, we show that purified recombinant PNP induces apoptosis in a dose dependent and cell type specific manner. Rat cardiac myoblasts (H9c2 cells) were more susceptible to the apoptotic promoting effects of PNP and ANP than HEK-293T cells where PNP had a protective effect at lower concentrations. Similarly rat thoracic myoblasts (A-10) were less responsive to both PNP and ANP than the H9c2 cells. Since PNP is mimicking the effect of ANP in this instance, PNP may prove to be a useful lead molecule for developing novel therapeutic natriuretic peptides.

摘要

心房利钠肽(ANP)在维持体液和血压的内稳态以及防止心肌肥厚和启动细胞凋亡过程中具有重要作用。十多年前,人们在植物中发现了一种具有免疫反应性的 ANP 类似物,并将其命名为植物利钠肽(PNP)。PNP 是一种小蛋白,含有与 ANP 相似的序列和结构,位于预测的突出 psi (psi) 环内。由于应用 ANP 或 PNP 可在植物中刺激相似的功能效应,因此可以想象 PNP 可能对哺乳动物细胞有影响。在本报告中,我们表明纯化的重组 PNP 以剂量依赖和细胞类型特异性的方式诱导细胞凋亡。大鼠心肌细胞(H9c2 细胞)比 HEK-293T 细胞更容易受到 PNP 和 ANP 的促凋亡作用的影响,而 PNP 在较低浓度下具有保护作用。同样,大鼠胸肌细胞(A-10)对 PNP 和 ANP 的反应性均低于 H9c2 细胞。由于在这种情况下 PNP 模拟了 ANP 的作用,因此 PNP 可能被证明是开发新型治疗性利钠肽的有用先导分子。

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