Cloning, in vitro expression, and tissue distribution of a human prostaglandin transporter cDNA (hPGT)

Cloning, in vitro expression, and tissue distribution of a human prostaglandin transporter cDNA (hPGT)
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DOI:
10.1172/jci118897
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发表时间:
1996-09-01
影响因子:
15.9
通讯作者:
Schuster, VL
Schuster, VL
中科院分区:
医学1区
文献类型:
--
作者:
Lu, R;Kanai, N;Schuster, VL

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我们最近在大鼠中发现了一个编码广泛表达的PG转运蛋白(PGT)的cDNA。由于前列腺素在人类健康和疾病中发挥着多种重要作用,我们从成人肾脏cDNA文库中克隆了人前列腺素转肽酶(hPGT)。来自几个克隆的共有序列(4.0 kb),加上3'聚合酶链反应扩增,与大鼠PGT相比,表现出74%的核酸同一性和82%的氨基酸同一性。当在HeLa细胞中瞬时表达时,全长克隆催化PGE(1)、PGE(2)、PGD(2)、PGF(2 α)的转运,并且在较小程度上催化TXB(2)的转运。北方印迹显示,在成人心脏、胎盘、脑、肺、肝、骨骼肌、胰腺、肾、脾、前列腺、卵巢、小肠和结肠中有许多不同大小的mRNA转录物。hPGT mRNA也在人胎儿脑、肺、肝和肾中强烈表达。hPGT的广泛组织分布和底物谱表明在多种人体组织中PG的转运和/或代谢清除中起作用。
We recently identified a cDNA in the rat that encodes a broadly expressed PG transporter (PGT). Because PGs play diverse and important roles in human health and disease, we cloned human PGT (hPGT) from an adult human kidney cDNA library. A consensus sequence (4.0 kb) derived from several clones, plus 3' polymerase chain reaction amplification, exhibited 74% nucleic acid identity and 82% amino acid identity compared to rat PGT. When transiently expressed in HeLa cells, a full-length clone catalyzed the transport of PGE(1), PGE(2), PGD(2), PGF(2 alpha) and, to a lesser degree TXB(2). Northern blotting revealed mRNA transcripts of many different sizes in adult human heart, placenta, brain, lung, liver, skeletal muscle, pancreas, kidney, spleen, prostate, ovary, small intestine, and colon. hPGT mRNAs are also strongly expressed in human fetal brain, lung, liver, and kidney. The broad tissue distribution and substrate profile of hPGT suggest a role in the transport and/or metabolic clearance of PGs in diverse human tissues.