Pratt R E, Flynn J A, Hobart P M, Paul M, Dzau V J
Molecular and Cellular Vascular Research Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115.
J Biol Chem. 1988 Mar 5;263(7):3137-41.
Mammalian cells in culture, transfected with human renin gene, can provide a useful tool for studying renin biosynthesis and secretion. We transfected fibroblast cells (mouse L929 and Chinese hamster ovary cells) and pituitary tumor cells (mouse AtT-20) with the human renin gene and a selectable plasmid (pSV2Neo). Transfected fibroblasts synthesize prorenin only. Prorenin is secreted by fibroblasts constitutively and the secretion is not influenced by 8-bromo-cAMP. On the other hand, transfected AtT-20 cells synthesized both prorenin and mature active renin. Transfected AtT-20 cells release prorenin by constitutive secretion but mature renin is secreted by a regulated mechanism since the secretion of the former is not influenced by 8-bromo-cAMP but the release of the latter is significantly stimulated. Our studies demonstrate that human renin may be secreted by at least two cellular pathways: prorenin by a constitutive pathway and mature renin by a regulated pathway. These transfected cells may provide useful models for studies of human renin synthesis, processing, and secretion.
用人类肾素基因转染的培养哺乳动物细胞，可为研究肾素的生物合成和分泌提供有用的工具。我们用人类肾素基因和一个可选择的质粒（pSV2Neo）转染了成纤维细胞（小鼠L929和中国仓鼠卵巢细胞）以及垂体肿瘤细胞（小鼠AtT-20）。转染后的成纤维细胞仅合成肾素原。肾素原由成纤维细胞组成型分泌，且这种分泌不受8-溴环磷酸腺苷的影响。另一方面，转染后的AtT-20细胞既合成肾素原也合成成熟的活性肾素。转染后的AtT-20细胞通过组成型分泌释放肾素原，但成熟肾素通过一种受调控的机制分泌，因为前者的分泌不受8-溴环磷酸腺苷的影响，而后者的释放则受到显著刺激。我们的研究表明，人类肾素可能至少通过两种细胞途径分泌：肾素原通过组成型途径，成熟肾素通过受调控的途径。这些转染细胞可能为研究人类肾素的合成、加工和分泌提供有用的模型。
