Institute of Biochemistry and Molecular Medicine, University of Bern, Bern, Switzerland.
Am J Physiol Regul Integr Comp Physiol. 2010 Aug;299(2):R642-54. doi: 10.1152/ajpregu.00723.2009. Epub 2010 May 5.
Members of the ATP-binding cassette (ABC) transporters play a pivotal role in cellular lipid efflux. To identify candidate cholesterol transporters implicated in lipid homeostasis and mammary gland (MG) physiology, we compared expression and localization of ABCA1, ABCG1, and ABCA7 and their regulatory genes in mammary tissues of different species during the pregnancy-lactation cycle. Murine and bovine mammary glands (MGs) were investigated during different functional stages. The abundance of mRNAs was determined by quantitative RT-PCR. Furthermore, transporter proteins were localized in murine, bovine, and human MGs by immunohistochemistry. In the murine MG, ABCA1 mRNA abundance was elevated during nonlactating compared with lactating stages, whereas ABCA7 and ABCA1 mRNA profiles were not altered. In the bovine MG, ABCA1, ABCG1, and ABCA7 mRNAs abundances were increased during nonlactating stages compared with lactation. Furthermore, associations between mRNA levels of transporters and their regulatory genes LXRalpha, PPARgamma, and SREBPs were found. ABCA1, ABCG1, and ABCA7 proteins were localized in glandular MG epithelial cells (MEC) during lactation, whereas during nonlactating stages, depending on species, the proteins showed distinct localization patterns in MEC and adipocytes. Our results demonstrate that ABCA1, ABCG1, and ABCA7 are differentially expressed between lactation and nonlactating stages and in association with regulatory genes. Combined expression and localization data suggest that the selected cholesterol transporters are universal MG transporters involved in transport and storage of cholesterol and in lipid homeostasis of MEC. Because of the species-specific expression patterns of transporters in mammary tissue, mechanisms of cholesterol homeostasis seem to be differentially regulated between species.
ATP 结合盒（ABC）转运蛋白家族成员在细胞脂质外排中发挥关键作用。为了鉴定参与脂质动态平衡和乳腺（MG）生理的候选胆固醇转运蛋白，我们比较了不同物种妊娠-泌乳周期中 ABCA1、ABCG1 和 ABCA7 及其调节基因在乳腺组织中的表达和定位。研究了鼠和牛乳腺（MG）在不同功能阶段的情况。通过定量 RT-PCR 确定 mRNA 的丰度。此外，通过免疫组织化学法在鼠、牛和人 MG 中定位转运蛋白。在鼠 MG 中，ABCA1 mRNA 的丰度在非泌乳期比泌乳期高，而 ABCA7 和 ABCA1 mRNA 谱没有改变。在牛 MG 中，ABCA1、ABCG1 和 ABCA7 mRNA 的丰度在非泌乳期比泌乳期增加。此外，还发现了转运蛋白及其调节基因 LXRalpha、PPARgamma 和 SREBPs 的 mRNA 水平之间存在关联。ABCA1、ABCG1 和 ABCA7 蛋白在泌乳期定位于乳腺上皮细胞（MEC），而在非泌乳期，根据物种的不同，蛋白在 MEC 和脂肪细胞中的定位模式不同。我们的研究结果表明，ABCA1、ABCG1 和 ABCA7 在泌乳和非泌乳期之间以及与调节基因的表达存在差异。结合表达和定位数据表明，所选胆固醇转运蛋白是参与胆固醇转运和储存以及 MEC 脂质动态平衡的通用 MG 转运蛋白。由于在乳腺组织中转运蛋白的物种特异性表达模式，胆固醇动态平衡的机制在不同物种之间似乎受到不同的调节。
