Rossi M A, Di Mauro C, Dianzani M U
Department of Experimental Medicine and Oncology, General Pathology Section, University of Turin, Turin, Italy.
Int J Tissue React. 2001;23(2):45-50.
The effects of three lipid peroxidation end-products, 4-hydroxynonenal (HNE), 2-nonenal (NE) and nonanal, on phosphoinositide-specific phospholipase C (PL-C) activity were studied in HL-60 cells. Enzymatic activity was determined by measuring the amounts of inositol-P3 (Ins-P3) produced by the cells incubated at 37 degrees C in the presence of the various compounds. HNE was shown to activate PL-C at concentrations of between 10(-8) and 10(-6) M; 10(-9) and 10(-8) M of NE also strongly stimulated PL-C. In contrast, nonanal failed to modify enzymatic activity. The concentrations of HNE and NE active on PL-C showed good correspondence with those that have been reported to be chemotactic towards rat neutrophils. The pretreatment of cells with 1 microM pertussis toxin completely prevented the increase of Ins-P3 production induced by HNE and NE. Maximal PL-C stimulation was produced by 10 nM NE; the degree of inositol-P3 production induced by the simultaneous addition of an equimolar dose of HNE was not significantly different from the activity value induced by NE alone, suggesting a possible competition between the two compounds. The data indicate that both HNE and NE share a common mechanism of action which, as with other better-known chemoattractants, involves PL-C activation through a G regulatory protein.
在HL-60细胞中研究了三种脂质过氧化终产物4-羟基壬烯醛（HNE）、2-壬烯醛（NE）和壬醛对磷酸肌醇特异性磷脂酶C（PL-C）活性的影响。通过测量在37℃下于各种化合物存在下孵育的细胞产生的肌醇-P3（Ins-P3）量来测定酶活性。结果显示，HNE在10^(-8)至10^(-6) M的浓度范围内可激活PL-C；10^(-9)至10^(-8) M的NE也强烈刺激PL-C。相比之下，壬醛未能改变酶活性。对PL-C有活性的HNE和NE的浓度与据报道对大鼠中性粒细胞有趋化作用的浓度显示出良好的对应关系。用1 microM百日咳毒素预处理细胞可完全阻止HNE和NE诱导的Ins-P3产生增加。10 nM NE产生最大的PL-C刺激；同时加入等摩尔剂量的HNE诱导的肌醇-P3产生程度与单独由NE诱导的活性值无显著差异，表明这两种化合物之间可能存在竞争。数据表明，HNE和NE都具有共同的作用机制，与其他更知名的趋化因子一样，涉及通过G调节蛋白激活PL-C。
