Kiss Z, Anderson W H
Hormel Institute, University of Minnesota, Austin 55912.
Arch Biochem Biophys. 1994 Jun;311(2):430-6. doi: 10.1006/abbi.1994.1258.
A major goal of this work was to determine in NIH 3T3 fibroblasts whether the recently described effects of H2O2 on phospholipase D-mediated hydrolysis of phosphatidylethanolamine (PtdEtn) and phosphatidylcholine (PtdCho) are mediated by similar or different mechanisms. While exposure of NIH 3T3 fibroblasts to H2O2 stimulated the hydrolysis of both PtdEtn and PtdCho, the following important differences were noted: (i) prolonged (24 h) treatment of fibroblasts with 400 nM phorbol 12-myristate 13-acetate (PMA) blocked the stimulatory effect of H2O2 on PtdEtn, but not on PtdCho, hydrolysis; (ii) PMA-induced hydrolysis of PtdEtn, but not PtdCho, was inhibited by H2O2; (iii) the stimulatory effect of H2O2 was additive with that of sphingosine or staurosporine, inhibitors of protein kinase C, on the hydrolysis of PtdCho, but not PtdEtn; (iv) with membranes isolated from H2O2-treated fibroblasts, the hydrolysis of PtdCho, but not PtdEtn, was increased compared to values obtained with control membranes. These results imply that H2O2 regulates PtdEtn and PtdCho hydrolysis by different mechanisms. Stimulation of PtdEtn hydrolysis by H2O2, sphingosine, and staurosporine may commonly involve, at least in part, neutralization of an inhibitory protein kinase C isozyme.
这项工作的一个主要目标是在NIH 3T3成纤维细胞中确定，过氧化氢（H2O2）最近所描述的对磷脂酶D介导的磷脂酰乙醇胺（PtdEtn）和磷脂酰胆碱（PtdCho）水解的影响是由相似还是不同的机制介导的。虽然将NIH 3T3成纤维细胞暴露于H2O2会刺激PtdEtn和PtdCho的水解，但注意到了以下重要差异：（i）用400 nM佛波醇12 - 肉豆蔻酸酯13 - 乙酸酯（PMA）对成纤维细胞进行长时间（24小时）处理可阻断H2O2对PtdEtn水解的刺激作用，但不影响对PtdCho水解的刺激作用；（ii）H2O2抑制PMA诱导的PtdEtn水解，但不抑制PtdCho水解；（iii）H2O2的刺激作用与鞘氨醇或星形孢菌素（蛋白激酶C的抑制剂）对PtdCho水解的刺激作用具有加和性，但对PtdEtn水解无此作用；（iv）与从经H2O2处理的成纤维细胞分离的膜相比，与对照膜相比，PtdCho的水解增加，但PtdEtn的水解未增加。这些结果表明，H2O2通过不同机制调节PtdEtn和PtdCho的水解。H2O2、鞘氨醇和星形孢菌素对PtdEtn水解的刺激作用可能至少部分共同涉及一种抑制性蛋白激酶C同工酶的中和。
