title: p38α subtype is a potential target to inhibit eNOS activity and NO production in human endothelial cells.
abstract: Human endothelial nitric oxide synthase (eNOS) activity is important for maintaining blood pressure homeostasis and vascular integrity through nitric oxide (NO).The in vitro study aimed at investigating a role of p38α signaling in modulating NO production in human umbilical vein endothelial cell-12 (HUVEC-12). Consistent with the stimulation of lipopolysaccharide (LPS) or tumor necrosis factor (TNF)-α, the over-expression of p38α markedly down-regulated the eNOS promoter activity in HUVEC-12, which could be reversed by its negative mutant p38α (AF) or p38-specific inhibitor SB203580. Compared to the stimulation of LPS or TNF-α, p38α-targeting siRNA decreased the expressions of phosphorylated and non-phosphorylated p38α, and increased the promoter activity, an eNOS mRNA level and a phosphorylated eNOS protein expression with the enhancement of NO, which could be abrogated by the scrambled siRNA. The in situ eNOS protein expression in the cells treated by p38α-targeting siRNA was also higher than that of the control, following the corresponding attenuation of a p38 level, and mainly localized in the inner membrane and cytoplasm. These results indicate that the p38α subtype may be a potential target to down-regulate the eNOS activity and NO production in human endothelial cells.
authors.affiliation: Department of Immunobiology, Jinan University, Guangzhou 510632, China.
authors.forename: Baoyu
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Immunobiology, Jinan University, Guangzhou 510632, China; Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Jinan University, Guangzhou 510632, China. Electronic address: tfyxing@jnu.edu.cn.
authors.forename: Feiyue
authors.initials: F
authors.lastname: Xing
authors.affiliation: Department of Immunobiology, Jinan University, Guangzhou 510632, China.
authors.forename: Na
authors.initials: N
authors.lastname: Liu
authors.affiliation: Department of Immunobiology, Jinan University, Guangzhou 510632, China.
authors.forename: Dingwu
authors.initials: D
authors.lastname: Chen
authors.affiliation: Department of Immunobiology, Jinan University, Guangzhou 510632, China.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Stomatology, Jinan University School of Medicine, Guangzhou 510632, China. Electronic address: tjliu@jnu.edu.cn.
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
mesh_terms: D001794:Blood Pressure; D003593:Cytoplasm / Q000378:metabolism; D015536:Down-Regulation; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic; D006706:Homeostasis; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D048308:Mitogen-Activated Protein Kinase 14 / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D010766:Phosphorylation; D011725:Pyridines / Q000494:pharmacology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D007093:Imidazoles; D008070:Lipopolysaccharides; D011725:Pyridines; D034741:RNA, Small Interfering; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D048308:Mitogen-Activated Protein Kinase 14; C093642:SB 203580