Docosahexaenoic acid prevented tumor necrosis factor alpha-induced endothelial dysfunction and senescence

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• 作者：Kazuo Yamagata^a ; ^{kyamagat@brs.nihon-u.ac.jp" class="auth_mail" title="E-mail the corresponding author} ; Sayaka Suzuki^a ; Motoki Tagami^b
• 关键词：DHA ; docosahexaenoic acid ; ICAM-1 ; intercellular adhesion molecule-1 ; LOX1 ; lectin-like oxidized low-density lipoprotein receptor-1 ; TXA2R ; thromboxane A2 receptor ; TNF-α ; tumor necrosis factor-alpha ; PAI-1 ; plasminogen activator inhibitor-1 ; eNOS ; endothelial nitric oxide synthase ; ROS ; reactive oxygen species ; VCAM-1 ; vascular cell adhesion molecule-1 ; VEGF ; vascular endothelial growth factor
• 刊名：Prostaglandins, Leukotrienes and Essential Fatty Acids
• 出版年：2016
• 出版时间：January 2016
• 年：2016
• 卷：104
• 期：Complete
• 页码：11-18
• 全文大小：1861 K

文摘

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.