VIP 和催产素的生物合成和功能：C 端酰胺化、催产素分泌和运输的机制。,Endocrinology

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VIP 和催产素的生物合成和功能：C 端酰胺化、催产素分泌和运输的机制。
Endocrinology ( IF 3.8 ) Pub Date : 2023-08-01 , DOI: 10.1210/endocr/bqad121
Hideto Yonekura _{1,

2} , Ichiro Kato _{2,

3} , Yasuhiko Yamamoto _{2,

4} , Takayuki Ikeda _{1,

2} , Haruhiro Higashida ₅ , Hiroshi Okamoto _{2,

3,

4}

Affiliation

在这篇综述中，我们提供了血管活性肠肽（VIP）和催产素这两种典型的C端α-酰胺化肽激素的研究现状，包括它们的前体蛋白结构、加工和C端α-酰胺化，以及最近发现的机制催产素分泌及其通过血脑屏障运输的调节。超过一半的神经肽和内分泌肽，例如 VIP 和催产素，其 C 末端具有 α-酰胺结构，这对于生物活性至关重要。自 20 世纪 80 年代以来，我们一直在研究 C 端 α-酰胺化肽（包括 VIP 和催产素）的合成和功能。人VIP mRNA不仅编码VIP，还编码另一种相关的C端α-酰胺化肽PHM-27（具有氨基端组氨酸、羧基端甲硫氨酸酰胺和27个氨基酸残基的肽）。人类VIP/PHM-27基因由7个外显子组成，并受到环AMP和蛋白激酶C途径的协同调节。VIP 在使用转基因小鼠技术的血糖控制中发挥着重要作用。肽 C 端 α-酰胺化通过由单个 mRNA 中编码的 2 种不同酶催化的两步机制进行。在下丘脑/垂体后叶的催产素分泌中，CD38-环状ADP-核糖信号系统被发现是必不可少的，该系统最初是在朗格汉斯胰岛的胰腺β细胞的胰岛素分泌中建立的。还提出了一种可能的机制，涉及催产素通过血脑屏障从血流运输到大脑的 RAGE（晚期糖基化终产物受体）。

"点击查看英文标题和摘要"

Biosynthesis and Function of VIP and Oxytocin: Mechanisms of C-terminal Amidation, Oxytocin Secretion and Transport.

In this review, we provide the status of research on vasoactive intestinal peptide (VIP) and oxytocin, typical C-terminal α-amidated peptide hormones, including their precursor protein structures, processing and C-terminal α-amidation, and the recently identified mechanisms of regulation of oxytocin secretion and its transportation through the blood brain barrier. More than half of neural and endocrine peptides, such as VIP and oxytocin, have the α-amide structure at their C-terminus, which is essential for biological activities. We have studied the synthesis and function of C-terminal α-amidated peptides, including VIP and oxytocin, since the 1980s. Human VIP mRNA encoded not only VIP but also another related C-terminal α-amidated peptide, PHM-27 (peptide having amino-terminal histidine, carboxy-terminal methionine amide, and 27 amino acid residues). The human VIP/PHM-27 gene is composed of 7 exons and regulated synergistically by cyclic AMP and protein kinase C pathways. VIP has an essential role in glycemic control using transgenic mouse technology. The peptide C-terminal α-amidation proceeded through a 2-step mechanism catalyzed by 2 different enzymes encoded in a single mRNA. In the oxytocin secretion from the hypothalamus/the posterior pituitary, the CD38-cyclic ADP-ribose signal system, which was first established in the insulin secretion from pancreatic β cells of the islets of Langerhans, was found to be essential. A possible mechanism involving RAGE (receptor for advanced glycation end-products) of the oxytocin transportation from the blood stream into the brain through the blood-brain barrier has also been suggested.

更新日期：2023-08-01

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