title: Docosahexaenoic acid prevented tumor necrosis factor alpha-induced endothelial dysfunction and senescence.
abstract: We investigated how docosahexaenoic acid (DHA) regulated tumor necrosis factor-alpha (TNF-α)-induced senescence and dysfunction in endothelial cells (EC). We used RT-PCR to examine the expression of several genes related to senescence and dysfunction in EC. TNF-α-induced p21 protein levels were investigated by Western blot (WB) and fluorescence antibody techniques. TNF-α induced the senescence marker β-galactosidase and the expression of several senescence and endothelial dysfunction-related genes, e.g., CDKN1A, SHC1 and GLB1. DHA attenuated TNF-α-induced senescence-related gene expression and p21 protein expression. DHA attenuated TNF-α-induced gene expression related to dysfunction of EC, such as plasminogen activator inhibitor 1 (SERPINE1), lectin-like oxidized low-density lipoprotein receptor-1 (OLR1), thromboxane A2 receptor (TXA2R) and p38 MAPK (MAPK14). DHA reversed the TNF-α-mediated reduction of endothelial nitric oxide synthase (NOS3) gene expression. TNF-α-mediated upregulation of these genes was inhibited by allopurinol and apocynin. These results indicated that DHA regulated the expression of several genes that are associated with senescence and dysfunction of EC.
authors.affiliation: Department of Food Bioscience and Biotechnology, College of Bioresource Sciences, Nihon University (NUBS), Fujisawa, Japan. Electronic address: kyamagat@brs.nihon-u.ac.jp.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Yamagata
authors.affiliation: Department of Food Bioscience and Biotechnology, College of Bioresource Sciences, Nihon University (NUBS), Fujisawa, Japan.
authors.forename: Sayaka
authors.initials: S
authors.lastname: Suzuki
authors.affiliation: Department of Internal Medicine, Sanraku Hospital, Chiyoda-Ku, Tokyo, Japan.
authors.forename: Motoki
authors.initials: M
authors.lastname: Tagami
mesh_terms: D002460:Cell Line; D016922:Cellular Senescence / Q000187:drug effects*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D051127:Scavenger Receptors, Class E / Q000378:metabolism; D055765:Shc Signaling Adaptor Proteins / Q000378:metabolism; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; C495137:OLR1 protein, human; D017395:Plasminogen Activator Inhibitor 1; C051321:SERPINE1 protein, human; C528024:SHC1 protein, human; D051127:Scavenger Receptors, Class E; D055765:Shc Signaling Adaptor Proteins; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D014409:Tumor Necrosis Factor-alpha; D004281:Docosahexaenoic Acids; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; C061901:GLB1 protein, human; D001616:beta-Galactosidase
keywords: DHA; Dysfunction; Endothelial cells; Senescence; TNFα