Robison T W, Forman H J
Department of Pediatrics, University of Southern California, Childrens Hospital, Los Angeles 90027.
Prostaglandins. 1990 Jul;40(1):13-28. doi: 10.1016/0090-6980(90)90053-x.
Rat alveolar macrophages, labeled with 3H-arachidonic acid, were treated with t-butyl hydroperoxide (tBOOH). Treatment of cells with 100 microM tBOOH led to a rapid increase in 12-hydroxyheptadecatrienoic acid (12-HHT) within 2.5 minutes. At 15 minutes, 12-HHT levels appeared to plateau as there was no further increase at 30 minutes. TxB2 levels increased in a similar manner to that found with 12-HHT; however, only the level at 15 minutes was statistically increased. TxB2 levels also appeared to plateau at 15 minutes. Indomethacin, at a concentration of 1 microM, significantly inhibited TxB2 and 12-HHT production by approximately 90%. Desferal, an iron chelator, had no effect on alterations of biosynthesis of cyclooxygenase products by macrophages treated with tBOOH. No evidence of lipoxygenase products was found. Thus, these results suggest that tBOOH rapidly and selectively stimulated arachidonic acid metabolism through the cyclooxygenase pathway in rat alveolar macrophages. The stimulation of cyclooxygenase activity was transient with a maximum rate observed at 100 microM tBOOH.
用3H - 花生四烯酸标记的大鼠肺泡巨噬细胞，用叔丁基过氧化氢（tBOOH）处理。用100微摩尔/升的tBOOH处理细胞后，在2.5分钟内12 - 羟基十七碳三烯酸（12 - HHT）迅速增加。15分钟时，12 - HHT水平似乎达到平台期，因为30分钟时没有进一步增加。血栓素B2（TxB2）水平的增加方式与12 - HHT相似；然而，只有15分钟时的水平有统计学意义的增加。TxB2水平在15分钟时也似乎达到平台期。浓度为1微摩尔/升的吲哚美辛显著抑制TxB2和12 - HHT的产生约90%。去铁胺，一种铁螯合剂，对用tBOOH处理的巨噬细胞环氧合酶产物生物合成的改变没有影响。未发现脂氧合酶产物的证据。因此，这些结果表明，tBOOH在大鼠肺泡巨噬细胞中通过环氧合酶途径迅速且选择性地刺激花生四烯酸代谢。环氧合酶活性的刺激是短暂的，在100微摩尔/升的tBOOH时观察到最大速率。
