Ji C M, Cardoso W V, Gebremichael A, Philpot R M, Buckpitt A R, Plopper C G, Pinkerton K E
Department of Anatomy, Physiology, and Cell Biology, School of Veterinary Medicine, University of California, Davis 95616, USA.
Am J Physiol. 1995 Sep;269(3 Pt 1):L394-402. doi: 10.1152/ajplung.1995.269.3.L394.
Because a number of studies suggest that the developmental expression of cytochrome P-450s (CYP) in Clara cells is species specific, this study was designed to compare the developmental patterns of the isoform CYP2B and NADPH reductase protein expression and CYP2B activity with the time course of smooth endoplasmic reticulum (SER) formation in Clara cells of rat lung. Pulmonary CYP2B activity measured as pentoxyresorufin O-dealkylation in lung homogenates was not detectable before 7 days postnatal age, but was detectable at adult levels at 50 days postnatal age. In Clara cells, CYP2B and NADPH reductase were detected immunohistochemically at 4 days postnatal age and at adult levels at 10 days postnatal age. The volume density of SER in Clara cells of terminal bronchioles measured morphometrically increased significantly with postnatal age. We conclude that in the rat 1) CYP2B and NADPH reductase distribution and CYP2B activity are age dependent; 2) the increase in Clara cell SER precedes the expression of CYP2B protein; 3) cellular appearance of CYP2B protein precedes CYP activity; and 4) SER appearance and P-450 protein expression do not occur uniformly in differentiating Clara cells, even within the same bronchiole.
由于多项研究表明，克拉拉细胞中细胞色素P-450（CYP）的发育表达具有物种特异性，本研究旨在比较大鼠肺克拉拉细胞中CYP2B同工型、NADPH还原酶蛋白表达和CYP2B活性的发育模式与滑面内质网（SER）形成的时间进程。以肺匀浆中戊氧基试卤灵O-脱烷基化来衡量的肺CYP2B活性在出生后7天前无法检测到，但在出生后50天达到成年水平时可检测到。在克拉拉细胞中，免疫组织化学检测显示出生后4天可检测到CYP2B和NADPH还原酶，出生后10天达到成年水平。通过形态计量学测量，终末细支气管克拉拉细胞中SER的体积密度随出生后年龄显著增加。我们得出结论，在大鼠中：1）CYP2B和NADPH还原酶的分布以及CYP2B活性与年龄有关；2）克拉拉细胞SER的增加先于CYP2B蛋白的表达；3）CYP2B蛋白的细胞出现先于CYP活性；4）即使在同一细支气管内，分化中的克拉拉细胞中SER的出现和P-450蛋白的表达也并非均匀发生。
