Oxidized LDL at low concentration promotes in-vitro angiogenesis and activates nitric oxide synthase through PI3K/Akt/eNOS pathway in human coronary artery endothelial cells |
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Authors: | Yu Shan Wong Siu Ling Lau Chi Wai Huang Yu Yu Cheuk-Man |
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Institution: | aInterdisciplinary Research Organization, University of Miyazaki, Miyazaki 889-1692, Japan;bDepartment of Biology, School of Medicine, Kurume University, Fukuoka 830-0011, Japan;cMolecular Genetics, Institute of Life Sciences, Kurume University, Fukuoka 839-0864, Japan;dDepartment of Stem Cell Biology, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto 860-0811, Japan;ePeptide Institute Inc., Osaka 567-0085, Japan;fFrontier Science Research Center, University of Miyazaki, Miyazaki 889-1692, Japan;gDepartment of Veterinary Physiology, Faculty of Agriculture, University of Miyazaki, Miyazaki 889-2155, Japan;hDepartment of Biochemistry, National Cerebral and Cardiovascular Center Research Institute, Osaka 565-8565, Japan |
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Abstract: | There are many orphan G protein-coupled receptors (GPCRs), for which ligands have not yet been identified, in both vertebrates and invertebrates, such as Drosophila melanogaster. Identification of their cognate ligands is critical for understanding the function and regulation of such GPCRs. Indeed, the discovery of bioactive peptides that bind GPCRs has enhanced our understanding of mechanisms underlying many physiological processes. Here, we identified an endogenous ligand of the Drosophila orphan GPCR, CG34381. The purified ligand is a peptide comprised of 28 amino acids with three intrachain disulfide bonds. The preprotein is coded for by gene CG14871. We designated the cysteine-rich peptide “trissin” (it means for triple S–S bonds) and characterized the structure of intrachain disulfide bonds formation in a synthetic trissin peptide. Because the expression of trissin and its receptor is reported to predominantly localize to the brain and thoracicoabdominal ganglion, trissin is expected to behave as a neuropeptide. The discovery of trissin provides an important lead to aid our understanding of cysteine-rich peptides and their functional interaction with GPCRs. |
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Keywords: | Abbreviations: GPCRs G protein-coupled receptors CHO Chinese hamster ovary CM carboxymethyl ACN acetonitrile TFA trifluoroacetic acid PTH phenyl thiohydantoin |
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