Yu M, Jamieson G A, Leikauf G D, Nebert D W
University of Cincinnati Medical Center, Ohio 45267-0056, USA.
Biochem Pharmacol. 1998 Jan 15;55(2):193-200. doi: 10.1016/s0006-2952(97)00418-8.
This laboratory has previously shown that increases in the expression of several genes in SV40-transformed hepatocyte cultures derived from the untreated newborn c14CoS/c14CoS mouse, and in newborn mouse liver--when compared with the cch/cch wild-type--are associated with enhanced levels of reactive oxygenated metabolites (ROMs) and reduced glutathione (GSH). We show here that, in contrast to the ch/ch wild-type levels, the oxidatively stressed 14CoS/14CoS liver cell line displays 2- to 5-fold increases in 1) phospholipase A2 (PLA2) enzyme activity, 2) Ca2+ dependent Group II secreted PLA2 mRNA levels, 3) arachidonic acid release, and 4) arachidonic acid metabolites co-eluting with prostaglandins D2, E2, and F2 alpha. These findings suggest that the cyclooxygenase-2 (COX2) pathway, and possible involvement of the "inflammatory" and/or "acute phase response" signal transduction pathways, might be activated during the endogenous ROM-mediated oxidative stress response in 14CoS/14CoS cells.
本实验室先前已表明，与cch/cch野生型相比，源自未经处理的新生c14CoS/c14CoS小鼠的SV40转化肝细胞培养物以及新生小鼠肝脏中几种基因表达的增加与活性氧化代谢物（ROMs）水平升高和谷胱甘肽（GSH）减少有关。我们在此表明，与ch/ch野生型水平相比，氧化应激的14CoS/14CoS肝细胞系在以下方面表现出2至5倍的增加：1）磷脂酶A2（PLA2）酶活性；2）钙依赖性II型分泌型PLA2 mRNA水平；3）花生四烯酸释放；4）与前列腺素D2、E2和F2α共洗脱的花生四烯酸代谢物。这些发现表明，在14CoS/14CoS细胞内源性ROM介导的氧化应激反应过程中，环氧合酶-2（COX2）途径以及“炎症”和/或“急性期反应”信号转导途径可能被激活。
