Novel roles of neuropeptide processing enzymes: EC3.4.24.15 in the neurome.
Novel roles of neuropeptide processing enzymes: EC3.4.24.15 in the neurome.
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神经肽加工酶的新作用：神经元中的 EC3.4.24.15。
DOI：
10.1002/jnr.10779
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发表时间：
2003
期刊：
影响因子：
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通讯作者：
Glucksman,MJ
中科院分区：
文献类型：
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作者：
Kim,SI;Grum-Tokars,V;Swanson,TA;Cotter,EJ;Cahill,PA;Roberts,JL;Cummins,PM;Glucksman,MJ
神经肽加工金属酶，如血管紧张素转换酶、Neprilysin、内皮素转换酶、Neurolysin和EC3.4.24.15(EP24.15)，是生物活性多肽形成和降解的中心。我们将EP24.15作为神经酶中这些酶的新功能的范例。虽然神经酶通常包括大脑和中枢神经系统的蛋白质组，但这些神经肽酶令人兴奋的新作用已经在其他器官系统中得到证明。我们讨论EP24.15与临床后遗症的关系，包括使用促性腺激素释放激素(GnRH；LHRH)类似物作为酶抑制剂，在血管生理学(血压调节)和血液系统(免疫监测)中的作用。循环应变和剪切力等血流动力作用于血管细胞，可诱导EP24.15转录增加，提示神经肽酶介导的升压/降压肽的水解可能受血流动力和血压变化的调节。最后，EP24.15在体内调节主要组织相容性复合体第I类蛋白的表面表达，提示EP24.15可能在内源性表达增加的部位维持免疫赦免方面发挥重要作用。在这些神经外系统中，神经肽酶对神经肽和其他多肽底物的调节表明，这些酶的影响可能比先前预期的更具全局性，并表明它们作为神经肽酶的归属作用低估了它们在神经系统中的生理作用。©2003 Wiley-Liss公司
Neuropeptide processing metalloenzymes, such as angiotensin converting enzyme, neprilysin, endothelin converting enzyme, neurolysin, and EC3.4.24.15 (EP24.15), are central to the formation and degradation of bioactive peptides. We present EP24.15 as a paradigm for novel functions ascribed to these enzymes in the neurome. Although the neurome typically encompasses proteomes of the brain and central nervous system, exciting new roles of these neuropeptidases have been demonstrated in other organ systems. We discuss the involvement of EP24.15 with clinical sequelae involving the use of gonadotropin‐releasing hormone (GnRH; LHRH) analogs that act as enzyme inhibitors, in vascular physiology (blood pressure regulation), and in the hematologic system (immune surveillance). Hemodynamic forces, such as cyclic strain and shear stress, on vascular cells, induce an increase in EP24.15 transcription, suggesting that neuropeptidase‐mediated hydrolysis of pressor/depressor peptides is likely regulated by changes in hemodynamic force and blood pressure. Lastly, EP24.15 regulates surface expression of major histocompatibility complex Class I proteins in vivo, suggesting that EP24.15 may play an important role in maintenance of immune privilege in sites of increased endogenous expression. In these extraneural systems, regulation of both neuropeptide and other peptide substrates by neuropeptidases indicates that the influence of these enzymes may be more global than was anticipated previously, and suggests that their attributed role as neuropeptidases underestimates their physiologic actions in the neural system. © 2003 Wiley‐Liss, Inc.