Nagata K, Kiryu-Seo S, Kiyama H
Department of Anatomy and Neurobiology, Graduate School of Medicine, Osaka City University, Abeno-ku, Osaka 545-8585, Japan.
Neuroscience. 2006 Aug 11;141(1):299-310. doi: 10.1016/j.neuroscience.2006.03.032. Epub 2006 May 3.
Neuropeptides are crucial mediators in nervous and endocrine systems. Processing and degradation, the major regulatory mechanisms, of enzymes are essential for the control of these peptidergic intercellular signaling systems. Damage-induced neuronal endopeptidase (or endothelin converting enzyme-like1), a member of the neprilysin family, has recently been identified as an M13 zinc metalloprotease. Damage-induced neuronal endopeptidase mRNA expression is strikingly restricted to neurons, and is remarkably induced in response to various types of neuronal injuries, although its function and substrate remain unknown. To clarify the role of damage-induced neuronal endopeptidase, we examined the localization and ontogeny of damage-induced neuronal endopeptidase mRNA expression in the rat nervous system using in situ hybridization. Damage-induced neuronal endopeptidase mRNA was detected at embryonic day 12, and its expression restricted to the ventral region of the neural tube. Subsequently, expression was also apparent in primordia of the striatum, hypothalamus, and cranial motor nuclei during neural development. This specific distribution was relatively maintained in the adult brain, although expression levels became weaker. Expression of damage-induced neuronal endopeptidase was absent in the cerebral cortex, hippocampus, and cerebellum. In addition to prominent expression in CNS, intestinal and sensory ganglia and retina demonstrated transient intense damage-induced neuronal endopeptidase mRNA expression during the embryonic period that then declined, and disappeared after birth. The results indicated that damage-induced neuronal endopeptidase might play an important role in embryonic neural development, in particular in peripheral ganglia derived from the neural crest, and in some neurons originating from the basal plate such as the hypothalamus and cranial motor neurons.
神经肽是神经和内分泌系统中的关键介质。酶的加工和降解作为主要调节机制，对于控制这些肽能细胞间信号系统至关重要。损伤诱导的神经元内肽酶（或内皮素转化酶样 1）是中性内肽酶家族的成员，最近被鉴定为一种 M13 锌金属蛋白酶。损伤诱导的神经元内肽酶 mRNA 表达显著局限于神经元，并且在响应各种类型的神经元损伤时会显著诱导，尽管其功能和底物仍然未知。为了阐明损伤诱导的神经元内肽酶的作用，我们使用原位杂交技术研究了大鼠神经系统中损伤诱导的神经元内肽酶 mRNA 表达的定位和个体发生。在胚胎第 12 天检测到损伤诱导的神经元内肽酶 mRNA，其表达局限于神经管的腹侧区域。随后，在神经发育过程中，纹状体、下丘脑和颅运动核的原基中也出现了表达。这种特定分布在成年大脑中相对保持，尽管表达水平变弱。损伤诱导的神经元内肽酶在大脑皮层、海马体和小脑中不表达。除了在中枢神经系统中显著表达外，肠道和感觉神经节以及视网膜在胚胎期表现出短暂的强烈损伤诱导的神经元内肽酶 mRNA 表达，随后下降，并在出生后消失。结果表明，损伤诱导的神经元内肽酶可能在胚胎神经发育中起重要作用，特别是在源自神经嵴的外周神经节以及一些源自基板的神经元，如下丘脑和颅运动神经元中。
