title: Suppression of age-related renal changes in NF-kappaB and its target gene expression by dietary ferulate.
abstract: Ferulate is a well-described natural antioxidant found in plants. It protects against cellular redox disruption and several oxidative stress-related diseases, including inflammation in animal studies. In this study, we examined ferulate for its ability to suppress redox-sensitive, proinflammatory NF-kappaB activation via NF-kappaB-inducing kinase (NIK)/IkappaB kinase (IKK) and mitogen-activated protein kinases (MAPKs) by reducing oxidative stress in aged rats. The experimental design was set as follows: Sprague-Dawley rats, ages 7 months (young) and 20 months (old) were used in this study, and dietary ferulate (0.01% or 0.02%) was fed to the old rats for 10 days. Data show that in aged kidney tissue, ferulate exhibited its antioxidative action by maintaining redox regulation, suppressing NF-kappaB activation and modulating the expression of NF-kappaB-induced, proinflammatory COX-2, iNOS, VCAM-1 and ICAM-1. Next, we examined cultured YPEN-1 endothelial cells and show that ferulate protected YPEN-1 cells against tert-butylhydroperoxide-induced oxidative stress. The molecular modulation of NF-kappaB by ferulate was further revealed in endothelial YPEN-1 cells through ferulate's ability to suppress the activation of NIK/IKK and MAPKs. Based on these results, we conclude that ferulate's antioxidative capacity suppressed the age-related increase in NF-kappaB activity through inhibition of NIK/IKK and MAPKs in vivo. This study may also suggest the potentiality of ferulate as a developable supplement against chronic inflammatory disease as well as aging.
authors.affiliation: Virus Tumor Biology Section, Laboratory of Cellular Oncology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Kyung Jin
authors.initials: KJ
authors.lastname: Jung
authors.forename: Eun Kyung
authors.initials: EK
authors.lastname: Go
authors.forename: Ji Young
authors.initials: JY
authors.lastname: Kim
authors.forename: Byung Pal
authors.initials: BP
authors.lastname: Yu
authors.forename: Hae Young
authors.initials: HY
authors.lastname: Chung
mesh_terms: D000375:Aging / Q000187:drug effects / Q000502:physiology; D000818:Animals; D003373:Coumaric Acids / Q000494:pharmacology*; D004032:Diet; D005786:Gene Expression Regulation / Q000187:drug effects; D051550:I-kappa B Kinase / Q000096:biosynthesis; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D000097782:NF-kappaB-Inducing Kinase
chemical_list: D003373:Coumaric Acids; D051550:I-kappa B Kinase; D016328:NF-kappa B; D017346:Protein Serine-Threonine Kinases; D000097782:NF-kappaB-Inducing Kinase; C004999:ferulic acid