Golenkina Ekaterina A, Livenskyi Alexey D, Viryasova Galina M, Romanova Yulia M, Sud'ina Galina F, Sokolov Alexey V
a Lomonosov Moscow State University, Belozersky Institute of Physico-Chemical Biology, Moscow 119234, Russia.
b Gamaleya Research Institute of Epidemiology and Microbiology, Moscow 123098, Russia.
Biochem Cell Biol. 2017 Jun;95(3):445-449. doi: 10.1139/bcb-2016-0180. Epub 2017 Jan 10.
Ceruloplasmin, an acute-phase protein, can affect the activity of leukocytes through its various enzymatic activities and protein-protein interactions (with lactoferrin, myeloperoxidase, eosinophil peroxidase, serprocidins, and 5-lipoxygenase (5-LOX), among others). However, the molecular mechanisms of ceruloplasmin activity are not clearly understood. In this study, we tested the ability of two synthetic peptides, RPYLKVFNPR (883-892) (P1) and RRPYLKVFNPRR (882-893) (P2), corresponding to the indicated fragments of the ceruloplasmin sequence, to affect neutrophil activation. Leukotriene (LT) B4 is the primary eicosanoid product of polymorphonuclear leukocytes (PMNLs, neutrophils). We studied leukotriene synthesis in PMNLs upon interaction with Salmonella enterica serovar Typhimurium. Priming of neutrophils with phorbol 12-myristate 13-acetate (PMA) elicited the strong regulatory function of P2 peptide as a superoxide formation inducer and leukotriene synthesis inhibitor. Ceruloplasmin-derived P2 peptide appeared to be a strong inhibitor of 5-LOX product synthesis under conditions of oxidative stress.
铜蓝蛋白是一种急性期蛋白，可通过其多种酶活性以及蛋白质 - 蛋白质相互作用（与乳铁蛋白、髓过氧化物酶、嗜酸性粒细胞过氧化物酶、血清杀菌素和5 - 脂氧合酶（5-LOX）等相互作用）来影响白细胞的活性。然而，铜蓝蛋白活性的分子机制尚不清楚。在本研究中，我们测试了两种合成肽，即对应于铜蓝蛋白序列所示片段的RPYLKVFNPR（883 - 892）（P1）和RRPYLKVFNPRR（882 - 893）（P2）影响中性粒细胞活化的能力。白三烯（LT）B4是多形核白细胞（PMNLs，即中性粒细胞）产生的主要类花生酸产物。我们研究了PMNLs与肠炎沙门氏菌血清型鼠伤寒沙门氏菌相互作用时白三烯的合成情况。用佛波醇12 - 肉豆蔻酸酯13 - 乙酸酯（PMA）预处理中性粒细胞，引发了P2肽作为超氧化物形成诱导剂和白三烯合成抑制剂的强大调节功能。在氧化应激条件下，源自铜蓝蛋白的P2肽似乎是5-LOX产物合成的强效抑制剂。
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