Baybutt R C, Aziz S M, Fagerland J A, Olson J W, Gillespie M N
Division of Pharmacology and Experimental Therapeutics, College of Pharmacy, University of Kentucky, Lexington 40536-0082.
Toxicol Appl Pharmacol. 1994 Dec;129(2):188-95. doi: 10.1006/taap.1994.1243.
Lungs from monocrotaline (MCT)-treated rats exhibit altered polyamine metabolism and content. One of the prominent morphological abnormalities in MCT-treated lungs is a decrease in population density of type II pneumocytes. Against this background, the present study tested the hypothesis that failure to maintain normal population density of type II pneumocytes is associated with MCT-induced derangements in polyamine biosynthesis and/or transmembrane polyamine transport. After a 24-hr treatment, cultured type II pneumocytes exhibited numerous vacuoles at the highest dose of 3.2 mM MCT but not at the lower dose of 1.6 mM MCT. Intracellular spermidine content was significantly reduced at the highest dose of MCT. Relative to controls, the abundance of mRNA for both ornithine decarboxylase, and S-adenosylmethionine decarboxylase, key regulatory enzymes in polyamine synthesis, was not altered. However, the activities of both of these enzymes were dramatically reduced. Increased mRNA for the catabolic polyamine enzyme, spermine/spermidine-N1-acetyltransferase (SAT), paralleled significant increases in SAT activity. MCT also caused a concentration-related inhibition of spermidine uptake in type II cells, characterized by a fourfold decrease in Vmax with little change in Km. These results show that MCT alters type II pneumocyte polyamine regulatory mechanisms and may help explain the decreased population density of type II pneumocytes in MCT-treated rats.
用野百合碱（MCT）处理的大鼠肺脏表现出多胺代谢和含量的改变。MCT处理的肺脏中一个显著的形态学异常是II型肺细胞的群体密度降低。在此背景下，本研究检验了这样一个假设，即II型肺细胞未能维持正常的群体密度与MCT诱导的多胺生物合成和/或跨膜多胺转运紊乱有关。经过24小时的处理，培养的II型肺细胞在3.2 mM MCT的最高剂量下出现大量空泡，但在1.6 mM MCT的较低剂量下未出现。在MCT的最高剂量下，细胞内亚精胺含量显著降低。相对于对照组，多胺合成中的关键调节酶鸟氨酸脱羧酶和S-腺苷甲硫氨酸脱羧酶的mRNA丰度没有改变。然而，这两种酶的活性都显著降低。分解代谢多胺酶精胺/亚精胺-N1-乙酰转移酶（SAT）的mRNA增加，与SAT活性的显著增加平行。MCT还导致II型细胞中亚精胺摄取的浓度相关抑制，其特征是Vmax降低四倍，而Km变化不大。这些结果表明，MCT改变了II型肺细胞的多胺调节机制，可能有助于解释MCT处理的大鼠中II型肺细胞群体密度降低的原因。
