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• W2158487294 abstract "The bioactive component of mildly oxidized low-density lipoproteins, oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (OxPAPC), activates tissue factor expression and monocyte adhesion to endothelial cells (EC) from systemic circulation, but blocks expression of inflammatory adhesion molecules (VCAM, E-selectin) and neutrophil adhesion associated with EC acute inflammatory response to bacterial lypopolysacharide (LPS). Due to constant exposure to oxygen free radicals, lipids in the injured lung are especially prone to oxidative modification and increased OxPAPC generation. In this study, we focused on OxPAPC-mediated intracellular signaling mechanisms that lead to physiological responses in pulmonary endothelial cells. Our results demonstrate that OxPAPC treatment activated in a time-dependent fashion protein kinase C (PKC), protein kinase A (PKA), Raf/MEK1,2/Erk-1,2 MAP kinase cascade, JNK MAP kinase and transient protein tyrosine phosphorylation in human pulmonary artery endothelial cells (HPAEC), whereas nonoxidized PAPC was without effect. Pharmacological inhibition of PKC and tyrosine kinases blocked activation of Erk-1,2 kinase cascade upstream of Raf. OxPAPC did not affect myosin light chain (MLC) phosphorylation, but increased phosphorylation of cofillin, a molecular regulator of actin polymerization. Finally, OxPAPC induced p60Src-dependent tyrosine phosphorylation of focal adhesion proteins paxillin and FAK. Our results suggest a critical involvement of PKC and tyrosine phosphorylation in OxPAPC-induced activation of Erk-1,2 MAP kinase cascade associated with regulation of specific gene expression, and demonstrate rapid phosphorylation of cytoskeletal proteins, which indicates OxPAPC-induced EC remodeling." @default.
• W2158487294 created "2016-06-24" @default.
• W2158487294 creator A5010918611 @default.
• W2158487294 creator A5046940174 @default.
• W2158487294 creator A5051208927 @default.
• W2158487294 creator A5052491243 @default.
• W2158487294 date "2004-01-01" @default.
• W2158487294 modified "2023-10-15" @default.
• W2158487294 title "Signal transduction pathways activated in human pulmonary endothelial cells by OxPAPC, a bioactive component of oxidized lipoproteins" @default.
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• W2158487294 doi "https://doi.org/10.1016/j.mvr.2003.09.004" @default.
• W2158487294 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/14709399" @default.
• W2158487294 hasPublicationYear "2004" @default.
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