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牛固醇转运蛋白ABCG5和ABCG8的鉴定、序列分析及mRNA组织分布

Identification, sequence analysis and mRNA tissue distribution of the bovine sterol transporters ABCG5 and ABCG8.

作者信息

Viturro E, Farke C, Meyer H H D, Albrecht C

机构信息

Physiology Weihenstephan, Technical University Munich, Weihenstephaner Berg 3, 85354 Freising, Germany.

出版信息

J Dairy Sci. 2006 Feb;89(2):553-61. doi: 10.3168/jds.S0022-0302(06)72118-X.

DOI:10.3168/jds.S0022-0302(06)72118-X
PMID:16428624
Abstract

The family of ATP-binding cassette (ABC) transporters consists of several transmembrane proteins that use ATP hydrolysis as an energy source for the transport of a variety of substances through cellular membranes. Two members of this family, ABCG5 and ABCG8, are implicated in the intestinal absorption and biliar excretion of sterols. Cholesterol content in milk is highly variable among species, breeds, and individuals of the same species, but a potential application of these genes in lipid homeostasis in the mammary gland has never been addressed. In the present work, expression of ABCG5 and ABCG8 in the bovine was demonstrated for the first time and characterized by quantitative PCR. The entire coding region and promoter area were sequenced and screened for motifs involved in lipid homeostasis. Both ABCG5 and ABCG8 presented a high level of length and sequence identity with other mammalian species. In the intergenic promoter region, 2 GATA boxes, a liver receptor homolog-1 response element, and a nuclear factor-kappaB response element, important factors in other lipid regulatory processes, were identified. As expected, high expression levels of both ABCG5 and ABCG8 were present in liver and digestive tract samples, and interestingly, in the mammary gland, opening new avenues for further investigation about their potential role in lipid trafficking and excretion during lactation.

摘要

ATP结合盒(ABC)转运蛋白家族由几种跨膜蛋白组成,这些蛋白利用ATP水解作为能量来源,将多种物质转运穿过细胞膜。该家族的两个成员ABCG5和ABCG8与肠道对甾醇的吸收及胆汁对甾醇的排泄有关。牛奶中的胆固醇含量在不同物种、品种以及同一物种的个体之间差异很大,但这些基因在乳腺脂质稳态中的潜在应用从未被探讨过。在本研究中,首次证实了ABCG5和ABCG8在牛中的表达,并通过定量PCR对其进行了表征。对整个编码区和启动子区域进行了测序,并筛选了参与脂质稳态的基序。ABCG5和ABCG8与其他哺乳动物物种相比,在长度和序列上具有高度的一致性。在基因间启动子区域,鉴定出了2个GATA盒、1个肝脏受体同源物-1反应元件和1个核因子-κB反应元件,这些都是其他脂质调节过程中的重要因子。正如预期的那样,ABCG5和ABCG8在肝脏和消化道样本中均有高表达,有趣的是,在乳腺中也有高表达,这为进一步研究它们在泌乳期间脂质转运和排泄中的潜在作用开辟了新途径。

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