Suppression of age-related renal changes in NF-kappaB and its target gene expression by dietary ferulate.
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.
Jung
Kyung Jin
KJ
Virus Tumor Biology Section, Laboratory of Cellular Oncology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Go
Eun Kyung
EK
Kim
Ji Young
JY
Yu
Byung Pal
BP
Chung
Hae Young
HY
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
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