Ceruloplasmin-derived peptide is the strongest regulator of oxidative stress and leukotriene synthesis in neutrophils.
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.
a Lomonosov Moscow State University, Belozersky Institute of Physico-Chemical Biology, Moscow 119234, Russia.
Ekaterina A
EA
Golenkina
a Lomonosov Moscow State University, Belozersky Institute of Physico-Chemical Biology, Moscow 119234, Russia.
Alexey D
AD
Livenskyi
a Lomonosov Moscow State University, Belozersky Institute of Physico-Chemical Biology, Moscow 119234, Russia.
Galina M
GM
Viryasova
b Gamaleya Research Institute of Epidemiology and Microbiology, Moscow 123098, Russia.
Yulia M
YM
Romanova
a Lomonosov Moscow State University, Belozersky Institute of Physico-Chemical Biology, Moscow 119234, Russia.
Galina F
GF
Sud'ina
c FSBSI "Institute of Experimental Medicine", St. Petersburg 197376, Russia.|d Saint-Petersburg State University, St. Petersburg 199034, Russia.
Alexey V
AV
Sokolov
D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism; D016718:Arachidonic Acid / Q000378:metabolism; D002273:Carcinogens / Q000494:pharmacology; D002570:Ceruloplasmin / Q000378:metabolism*; D006801:Humans; D007975:Leukotriene B4 / Q000096:biosynthesis* / Q000276:immunology; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D010446:Peptide Fragments / Q000494:pharmacology*; D010587:Phagocytosis; D012486:Salmonella typhimurium / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D002273:Carcinogens; D010446:Peptide Fragments; D007975:Leukotriene B4; D016718:Arachidonic Acid; D001094:Arachidonate 5-Lipoxygenase; D002570:Ceruloplasmin; D013755:Tetradecanoylphorbol Acetate
5-lipoxygenase; 5-lipoxygénase; ceruloplasmin; céruloplasmine; myeloperoxidase; myéloperoxydase; neutrophil; neutrophile; superoxide; superoxyde