Colocalization of ghrelin O-acyltransferase and ghrelin in gastric mucosal cells

Colocalization of ghrelin O-acyltransferase and ghrelin in gastric mucosal cells
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DOI:
10.1152/ajpendo.90859.2008
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发表时间:
2009-07-01
影响因子:
5.1
通讯作者:
Zigman, Jeffrey M.
Zigman, Jeffrey M.
中科院分区:
医学2区
文献类型:
--
作者:
Sakata, Ichiro;Yang, Jing;Zigman, Jeffrey M.

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坂田 I、杨 J、李 CE、奥斯本-劳伦斯 S、罗文斯基 SA、埃尔姆奎斯特 JK、齐格曼 JM。胃粘膜细胞中胃饥饿素 O-酰基转移酶 (GOAT) 和胃饥饿素的共定位。 Am J Physiol Endocrinol Metab 297:E134-E141,2009。首次发表于 2009 年 4 月 28 日; doi: 10.1152/ajpendo.90859.2008.-Ghrelin 是一种肽激素,具有许多已知功能,包括促进食欲、血糖调节和抗抑郁作用等。成熟的生长素释放肽的独特之处在于,它是唯一已知的天然存在的肽,可通过辛酸的 O-酰化进行翻译后修饰。这种酰化是生长素释放肽的许多作用所必需的,包括其促进食物摄入和体重增加的作用。 GOAT(生长素释放肽 O-酰基转移酶)是膜结合 O-酰基转移酶 MBOAT 家族的 16 个成员之一,最近被鉴定为负责催化辛酰基添加至生长素释放肽的酶。尽管 GOAT 的初步报告已将其编码 mRNA 定位于已知含有生长素释放肽的组织,但目前尚不清楚辛酰化是否发生在生长素释放肽产生细胞内或邻近细胞中。在这里,我们对小鼠胃切片进行了双标记组织化学分析,并对高度富集的小鼠胃胃饥饿素细胞池中的 mRNA 进行了定量 PCR,以证明胃泌酸粘膜的胃饥饿素产生细胞内有高度的 GOAT mRNA 表达。我们还证明,GOAT 是 MBOAT 家族中唯一一个其表达在胃 ghrelin 细胞内高度富集且其全身分布与 ghrelin 相似的成员。
Sakata I, Yang J, Lee CE, Osborne-Lawrence S, Rovinsky SA, Elmquist JK, Zigman JM. Colocalization of ghrelin O-acyltransferase ( GOAT) and ghrelin in gastric mucosal cells. Am J Physiol Endocrinol Metab 297: E134-E141, 2009. First published April 28, 2009; doi: 10.1152/ajpendo.90859.2008.-Ghrelin is a peptide hormone with many known functions, including orexigenic, blood glucose-regulatory, and antidepressant actions, among others. Mature ghrelin is unique in that it is the only known naturally occurring peptide to be posttranslationally modified by O-acylation with octanoate. This acylation is required for many of ghrelin's actions, including its effects on promoting increases in food intake and body weight. GOAT ( ghrelin O-acyltransferase), one of 16 members of the MBOAT family of membrane-bound O-acyltransferases, has recently been identified as the enzyme responsible for catalyzing the addition of the octanoyl group to ghrelin. Although the initial reports of GOAT have localized its encoding mRNA to tissues known to contain ghrelin, it is as yet unclear whether the octanoylation occurs within ghrelin-producing cells or in neighboring cells. Here, we have performed dual-label histochemical analysis on mouse stomach sections and quantitative PCR on mRNAs from highly enriched pools of mouse gastric ghrelin cells to demonstrate a high degree of GOAT mRNA expression within ghrelin-producing cells of the gastric oxyntic mucosa. We also demonstrate that GOAT is the only member of the MBOAT family whose expression is highly enriched within gastric ghrelin cells and whose whole body distribution mirrors that of ghrelin.