The hippocampal cholinergic neurostimulating peptide, the N-terminal fragment of the secreted phosphatidylethanolamine-binding protein, possesses a new biological activity on cardiac physiology
The hippocampal cholinergic neurostimulating peptide, the N-terminal fragment of the secreted phosphatidylethanolamine-binding protein, possesses a new biological activity on cardiac physiology
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DOI：
10.1074/jbc.m308533200
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发表时间：
2004-03-26
影响因子：
4.8
通讯作者：
Metz-Boutigue, MH
中科院分区：
文献类型：
--
作者：
Goumon, Y;Angelone, T;Metz-Boutigue, MH
磷脂酰乙醇胺结合蛋白（PEBP），也称为Raf- 1激酶抑制蛋白，是海马胆碱能神经刺激肽（HCNP）的前体，对应于其天然N-末端片段，先前描述为由海马神经元释放. PEBP是一种可溶性细胞质蛋白，也与许多细胞类型的质膜和网膜相关。在本报告中，利用生物化学和细胞生物学技术，我们报告的PEBP在牛嗜铬细胞，一个良好的描述分泌模型的存在下，第一次。我们已经研究了它的存在下，在亚细胞水平上，其特征在于这种蛋白质的分泌颗粒膜和颗粒内基质。此外，据报道，其存在于牛嗜铬细胞和血小板胞吐培养基以及血清中，表明其是分泌的。与许多其他缺乏信号序列的蛋白质一样，PEBP可能通过非经典的信号分泌机制分泌，这可能是由于与颗粒膜脂质和脂筏的相互作用。通过二维液相色谱-串联质谱法，在颗粒内基质成分中检测到HCNP. PEBP和HCNP与儿茶酚胺一起分泌到循环中的观察促使我们研究这种肽对心血管系统的内分泌作用。通过使用作为生物测定的离体和灌流的青蛙（蛙）心脏制备，我们在这里表明，HCNP作用于心脏力学性能发挥负性肌力和抵消肾上腺素能刺激异丙肾上腺素。总之，这些数据表明，PEBP和HCNP可能被认为是参与心脏生理的新的内分泌因子。
Phosphatidylethanolamine- binding protein ( PEBP), alternatively named Raf- 1 kinase inhibitor protein, is the precursor of the hippocampal cholinergic neurostimulating peptide ( HCNP) corresponding to its natural N- terminal fragment, previously described to be released by hippocampal neurons. PEBP is a soluble cytoplasmic protein, also associated with plasma and reticulum membranes of numerous cell types. In the present report, using biochemistry and cell biology techniques, we report for the first time the presence of PEBP in bovine chromaffin cell, a well described secretion model. We have examined its presence at the subcellular level and characterized this protein on both secretory granule membranes and intragranular matrix. In addition, its presence in bovine chromaffin cell and platelet exocytotic medium, as well as in serum, was reported showing that it is secreted. Like many other proteins that lack signal sequence, PEBP may be secreted through non- classic signal secretory mechanisms, which could be due to interactions with granule membrane lipids and lipid rafts. By two- dimensional liquid chromatography- tandem mass spectrometry, HCNP was detected among the intragranular matrix components. The observation that PEBP and HCNP were secreted with catecholamines into the circulation prompted us to investigate endocrine effects of this peptide on cardiovascular system. By using as bioassay an isolated and perfused frog ( Rana esculenta) heart preparation, we show here that HCNP acts on the cardiac mechanical performance exerting a negative inotropism and counteracting the adrenergic stimulation of isoproterenol. All together, these data suggest that PEBP and HCNP might be considered as new endocrine factors involved in cardiac physiology.