title: Veratric acid inhibits iNOS expression through the regulation of PI3K activation and histone acetylation in LPS-stimulated RAW264.7 cells.
abstract: In the present study, we investigated regulatory effects of veratric acid on the production of nitric oxide (NO) in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. NO production was significantly decreased by veratric acid in the LPS-stimulated RAW264.7 cells in a dose-dependent manner. The reduction in nitric oxide production was induced by the downregulation of inducible NO synthase (iNOS) expression. Veratric acid suppressed the LPS-induced effects on the regulatory and catalytic subunits of phosphoinositide 3-kinase (PI3K), comprised of p85, p110α, p110β and Akt. The acetylation of p300 and the phosphorylation of activating transcription factor 2 (ATF-2) induced by LPS were downregulated following treatment with veratric acid; similar effects were observed following treatment with LY294002, a specific inhibitor of PI3K/Akt. The LPS-induced expression of histone deacetylase (HDAC)3 decreased to basal levels following treatment with veratric acid, and its expression was also downregulated by LY294002. In the measurement of histone acetylation levels, the LPS-stimulated acetylation of histone H4 was significantly attenuated by veratric acid, and was also reduced following the inhibition of PI3K/Akt with LY294002. From our data, it can be concluded that veratric acid exerts a regulatory effect on LPS-induced iNOS expression. Our results suggest that veratric acid impedes the PI3K/Akt-mediated histone acetyl-transferase (HAT) activation and HDAC expression induced by LPS, thereby abrogating iNOS expression.
authors.affiliation: Department of Microbiology, College of Natural Sciences, Pukyong National University, Busan 608-737, Republic of Korea.
authors.forename: Woo-Suk
authors.initials: WS
authors.lastname: Choi
authors.affiliation: Department of Microbiology, College of Natural Sciences, Pukyong National University, Busan 608-737, Republic of Korea.
authors.forename: Yong-Bae
authors.initials: YB
authors.lastname: Seo
authors.affiliation: Mushroom Research Division, National Institute of Horticultural and Herbal Science, Rural Development Administration, Suwon 441-707, Republic of Korea.
authors.forename: Pyung-Gyun
authors.initials: PG
authors.lastname: Shin
authors.affiliation: Division of Applied Life Science, Plant Molecular Biology and Biotechnology Research Center, Gyeongsang National University, Jinju 660-701, Republic of Korea.
authors.forename: Woe-Yeon
authors.initials: WY
authors.lastname: Kim
authors.affiliation: Division of Applied Life Science, Plant Molecular Biology and Biotechnology Research Center, Gyeongsang National University, Jinju 660-701, Republic of Korea.
authors.forename: Sang Yeol
authors.initials: SY
authors.lastname: Lee
authors.affiliation: Department of Food and Nutrition, College of Medical Life, Silla University, Busan 617-736, Republic of Korea.
authors.forename: Young-Ju
authors.initials: YJ
authors.lastname: Choi
authors.affiliation: Department of Microbiology, College of Natural Sciences, Pukyong National University, Busan 608-737, Republic of Korea.
authors.forename: Gun-Do
authors.initials: GD
authors.lastname: Kim
mesh_terms: D000107:Acetylation / Q000187:drug effects; D000818:Animals; D002460:Cell Line; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D008070:Lipopolysaccharides; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II / Q000235:genetics* / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D014641:Vanillic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D006657:Histones; D008070:Lipopolysaccharides; C009333:veratric acid; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D006655:Histone Deacetylases; D014641:Vanillic Acid