Mechanism of attenuation of pro-inflammatory Ang II-induced NF-κB activation by genistein in the kidneys of male rats during aging

Abstract

Angiotensin II (Ang II), a main effector of the renin-angiotensin system, is recognized as a pro-inflammatory mediator on age-related vascular inflammation. Ang II is one of the most important oxidative stress inducer, activates the redox-sensitive transcription factor, nuclear factor-κB (NF-κB) during aging. Genistein, a major component found in isoflavone, has anti-inflammatory activities that are often associated with its anti-oxidative activity. The purpose of this study is to document molecular mechanism of altered Ang II-related NF-κB activation during aging and inhibitory molecular events by genistein regarding to age-related Ang II-induced NF-κB activation. At present, we utilized young (6months old), old (24months old), and genistein-treated (2 and 4mg/kg/day for 10days) old rats. For our current study, we choose to use the kidney and rat endothelial cell line, YPEN-1 because of its vulnerability to age-related oxidative stress and inflammatory responsiveness. The results of the analysis showed that Ang II and AT1 expression increased during aging and that these increases were blunted by treatment with genistein. Furthermore, we investigated the inhibitory effects of genistein on the Ang II-induced redox imbalance in aged rat kidneys. Genistein reduced age-related increases in NF-κB activity and NF-κB-dependent pro-inflammatory genes expression. We also determined genistein attenuated Ang II-induced NF-κB activation through its anti-oxidant activity in YPEN-1 cells. Taken together, our present results show that genistein has potent anti-inflammatory effect resulting in the attenuation of the Ang II-induced NF-κB activation during aging. The most significant new finding from this study is that genistein exerts its anti-Ang II action during aging by suppressive effect of NF-κB activation. Based on these data, genistein may be an anti-Ang II agent that may be used in anti-inflammatory therapies.