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鉴定、克隆及醛酮还原酶 1B7 在两种撒哈拉沙漠啮齿动物(利比亚金仓鼠和沙漠跳鼠)肾上腺中的表达调控。

Identification, cloning and regulation of cDNA encoding aldo-keto reductase 1B7 in the adrenal gland of two Saharan rodents Meriones libycus (Libyan jird) and Gerbillus gerbillus (gerbil).

机构信息

Laboratoire de recherche sur les zones arides, Faculté des Sciences Biologiques, Université des Sciences et de la Technologie Houari Boumediene (USTHB), BP 44, Alger-Gare, 16000 DZ, Algeria.

出版信息

Gen Comp Endocrinol. 2011 Dec 1;174(3):292-300. doi: 10.1016/j.ygcen.2011.09.006. Epub 2011 Sep 22.

Abstract

Aldo-Keto Reductase 1B7 (AKR1B7) is a mouse aldose reductase-like protein with two major sites of expression, the vas deferens and the adrenal cortex. In the adrenal cortex, Akr1b7 is an adrenocorticotropin (ACTH)-responsive-gene whose product scavenges harmful byproducts of steroidogenesis and limits stress response through the biosynthesis of prostaglandin F2α. The purpose of the present study was to explore the possible expression of AKR1B7 in the adrenal glands of two saharan rodents, Libyan jird and Lesser Egyptian gerbil. Western blot analyses demonstrated that a protein related to murine/rat AKR1B7 was highly expressed in adrenals and absent from vas deferens of both saharan species. Based on conserved sequences between mouse and rat, full length cDNA were cloned and sequenced in both species while hormonal regulation and tissue localization were explored in Libyan jird. Both cDNA encoded the expected 316 amino acids protein typical of AKR1B subfamily and contained the highly conserved catalytic tetrad consisting in Asp-44, Tyr-49, Lys-78 and His-111 residues. The deduced proteins shared higher identities with aldose reductase-like, i.e. AKR1B7 (86-94%), AKR1B8 and AKR1B10 (83-86%) than with aldose reductase group, i.e. AKR1B1 and AKR1B3 (70%). Phylogenetic analysis showed that the Libyan jird and gerbil enzymes were more closely related to murine and rat AKR1B7 than to the other AKR1B members. Northern blot analyses of total RNA from Libyan jird adrenals showed a single mRNA transcript of 1.4 kb whose expression was dependent on circulating ACTH levels. In conclusion, we demonstrate here that adrenal glands of Libyan jird and gerbil express both an ortholog of the murine/rat Akr1b7 gene and that ACTH-responsiveness is at least conserved in Libyan jird.

摘要

醛酮还原酶 1B7(AKR1B7)是一种具有两个主要表达部位的鼠类醛糖还原酶样蛋白,即输精管和肾上腺皮质。在肾上腺皮质中,Akr1b7 是一种促肾上腺皮质激素(ACTH)反应基因,其产物可清除类固醇生成过程中的有害副产物,并通过前列腺素 F2α 的生物合成限制应激反应。本研究的目的是探索 AKR1B7 是否在两种撒哈啦啮齿动物——利比亚沙鼠和埃及小囊鼠的肾上腺中表达。Western blot 分析表明,一种与鼠/大鼠 AKR1B7 相关的蛋白在肾上腺中高度表达,而在两种撒哈啦物种的输精管中均不存在。根据鼠和大鼠之间的保守序列,在这两个物种中克隆并测序了全长 cDNA,并在利比亚沙鼠中探索了其激素调节和组织定位。这两种 cDNA 编码的预期 316 个氨基酸的蛋白质是 AKR1B 亚家族的典型代表,并且含有高度保守的催化四联体,由 Asp-44、Tyr-49、Lys-78 和 His-111 残基组成。推导的蛋白质与醛糖还原酶样蛋白(即 AKR1B7、AKR1B8 和 AKR1B10,86-94%)的相似度高于与醛糖还原酶组(即 AKR1B1 和 AKR1B3,70%)。系统进化分析表明,利比亚沙鼠和囊鼠的酶与鼠和大鼠 AKR1B7 更为密切相关,而与其他 AKR1B 成员关系较远。来自利比亚沙鼠肾上腺的总 RNA 的 Northern blot 分析显示,1.4kb 的单 mRNA 转录物的表达依赖于循环 ACTH 水平。总之,我们在这里证明,利比亚沙鼠和囊鼠的肾上腺均表达与鼠/大鼠 Akr1b7 基因的同源物,并且 ACTH 反应性至少在利比亚沙鼠中是保守的。

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