Sporn P H, Marshall T M, Peters-Golden M
Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor 48109-0360.
Biochim Biophys Acta. 1990 Nov 12;1047(2):187-91. doi: 10.1016/0005-2760(90)90046-z.
The dependence on protein kinase C (PKC) of arachidonic acid (AA) metabolism stimulated by the biologically important oxidant H2O2, as compared to zymosan particles, was investigated in the rat alveolar macrophage. The PKC inhibitor staurosporine markedly reduced AA release and eicosanoid synthesis stimulated by zymosan, but only slightly inhibited AA release and metabolism induced by H2O2. Furthermore, in macrophages depleted of PKC by extended exposure to phorbol 12-myristate 13-acetate, AA release in response to zymosan was greatly inhibited, whereas that stimulated by H2O2 was attenuated to a significantly lesser degree. Thus, zymosan-stimulated AA metabolism requires active PKC, whereas H2O2-induced metabolism is largely PKC-independent. This provides direct evidence for the existence of two pathways of agonist-stimulated AA metabolism, which differ in their dependence on PKC, in the alveolar macrophage.
在大鼠肺泡巨噬细胞中，研究了与酵母聚糖颗粒相比，具有生物学重要性的氧化剂过氧化氢（H₂O₂）刺激的花生四烯酸（AA）代谢对蛋白激酶C（PKC）的依赖性。PKC抑制剂星形孢菌素显著降低了酵母聚糖刺激的AA释放和类花生酸合成，但仅轻微抑制了H₂O₂诱导的AA释放和代谢。此外，通过长时间暴露于佛波酯12-肉豆蔻酸酯13-乙酸盐使PKC耗竭的巨噬细胞中，对酵母聚糖的反应性AA释放受到极大抑制，而H₂O₂刺激的AA释放仅在较小程度上减弱。因此，酵母聚糖刺激的AA代谢需要活性PKC，而H₂O₂诱导的代谢在很大程度上不依赖PKC。这为肺泡巨噬细胞中激动剂刺激的AA代谢存在两条途径提供了直接证据，这两条途径对PKC的依赖性不同。
