title: Down-regulation of histamine-induced endothelial cell activation as potential anti-atherosclerotic activity of peptides from Spirulina maxima.
abstract: Histamine, a potent inflammatory mediator, has been known to cause the pathogenesis of atherosclerosis. In this sense, two bioactive peptides P1 (LDAVNR; 686Da) and P2 (MMLDF; 655Da) purified from gastric enzymatic hydrolysate of Spirulina maxima were examined for their protective effects against early atherosclerotic responses induced by histamine in EA.hy926 endothelial cells. Interestingly, both P1 and P2 exhibited inhibitory activities on the production and expression of IL-6 and MCP-1. Furthermore, P1 and P2 inhibited the production of adhesion molecules including P-selectin and E-selectin, and thus reducing in vitro cell adhesion of monocyte onto endothelial cells. In addition, the production of intracellular reactive oxygen species was observed to reduce in the presence of P1 or P2. Notably, the inhibitory activities of P1 and P2 were found due to down-regulating Egr-1 expression via histamine receptor and PKCδ-dependent MAPKs activation pathway. These results suggest that peptides P1 and P2 from S. maxima are effective to suppress histamine-induced endothelial cell activation that may contribute to the prevention of early atherosclerosis.
authors.affiliation: Marine Bioprocess Research Center, Pukyong National University, Busan 608-737, Republic of Korea.
authors.forename: Thanh-Sang
authors.initials: TS
authors.lastname: Vo
authors.forename: Se-Kwon
authors.initials: SK
authors.lastname: Kim
mesh_terms: D050197:Atherosclerosis / Q000188:drug therapy; D002448:Cell Adhesion; D002460:Cell Line; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D051766:Early Growth Response Protein 1 / Q000235:genetics / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D006632:Histamine; D006633:Histamine Antagonists / Q000494:pharmacology*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology*; D011494:Protein Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D011968:Receptors, Histamine / Q000378:metabolism*; D053545:Spirulina; D020298:U937 Cells
chemical_list: C111835:CCL2 protein, human; D018932:Chemokine CCL2; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D006633:Histamine Antagonists; C508600:IL6 protein, human; D015850:Interleukin-6; D009842:Oligopeptides; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D011968:Receptors, Histamine; D006632:Histamine; D011494:Protein Kinases
keywords: Adhesion molecules; Atherosclerosis; Cytokine; Egr-1; Spirulina maxima