ABCA1 mRNA and protein distribution patterns predict multiple different roles and levels of regulation
ABCA1 mRNA and protein distribution patterns predict multiple different roles and levels of regulation
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DOI：
10.1038/labinvest.3780421
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发表时间：
2002-03-01
影响因子：
5
通讯作者：
Hayden, MR
中科院分区：
文献类型：
--
作者：
Wellington, CL;Walker, EKY;Hayden, MR
ABCA1突变导致等位基因紊乱、家族性低脂蛋白血症和丹吉尔病。为了确定ABCA1可能在哪里发挥功能作用，我们确定了小鼠ABCA1表达的细胞和组织特异性模式。对小鼠解剖组织的RT-PCR和Western blot分析表明，ABCA1 mRNA和蛋白在许多组织中广泛表达，在肝脏、睾丸和肾上腺组织中表达突出。原位杂交和免疫组织化学实验证实了ABCA1在细胞水平上的特异性表达模式，肝细胞、消化系统和膀胱上皮内膜、肾脏近曲小管以及浦肯野和皮质金字塔神经元中含有丰富的ABCA1蛋白。相对mRNA和蛋白表达模式之间的显著不一致表明ABCA1在特定细胞或组织中的表达可能存在转录后调控。我们还表明，暴露于致动脉粥样硬化饮食7天后，肝脏中的ABCA1蛋白水平特异性上调，支持肝脏在饮食调节HDL-C水平中的主要作用。我们的观察表明，ABCA1的表达模式与其在HDL-C代谢中的作用一致。此外，ABGA1可能在其他独立于HDL-C调节的细胞类型中具有重要的功能作用。
Mutations in ABCA1 cause the allelic disorders familial hypolipoproteinemia and Tangier Disease. To identify where ABCA1 was likely to have a functional role, we determined the cellular and tissue-specific patterns of murine ABCA1 expression. RT-PCR and Western blot analysis on dissected murine tissues demonstrated broad expression of ABCA1 mRNA and protein in many tissues with prominent protein expression in liver, testis, and adrenal tissue. In situ hybridization and immunohistochemistry experiments demonstrated specific patterns of ABCA1 expression at the cellular level, with hepatocytes, the epithelial lining of the digestive system and bladder, the proximal convoluted tubule of the kidney, and Purkinje and cortical pyramidal neurons containing abundant ABCA1 protein. Significant discordance between relative mRNA and protein expression patterns suggests the possibility of post-transcriptional regulation of ABCA1 expression in selected cells or tissues. We also show that ABCA1 protein levels are up-regulated specifically in the liver after exposure to an atherogenic diet for 7 days, supporting a major role for the liver in dietary modulation of HDL-C levels. Our observations show that ABCA1 is expressed in a pattern consistent with its role in HDL-C metabolism. Additionally, ABGA1 may have important functional roles in other cell types independent of HDL-C regulation.