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Mechanism of Ang II involvement in activation of NF-kappaB through phosphorylation of p65 during aging.

Authors: Kim, JM  Heo, HS  Ha, YM  Ye, BH  Lee, EK  Choi, YJ  Yu, BP  Chung, HY 
Citation: Kim JM, etal., Age (Dordr). 2011 Feb 12.
Pubmed: (View Article at PubMed) PMID:21318332
DOI: Full-text: DOI:10.1007/s11357-011-9207-7

Angiotensin II (Ang II), a major effector of the renin-angiotensin system, is now recognized as a pro-inflammatory mediator. This Ang II signaling, which causes transcription of pro-inflammatory genes, is regulated through nuclear factor-kappaB (NF-kappaB). At present, the molecular mechanisms underlying the effect of aging on Ang II signaling and NF-kappaB activation are not fully understood. The purpose of this study was to document altered molecular events involved in age-related changes in Ang II signaling and NF-kappaB activation. Experimentations were carried out using kidney tissues from Fischer 344 rats at 6, 12, 18, and 24 months of age, and the rat endothelial cell line, YPEN-1 for the detailed molecular work. Results show that increases in Ang II and Ang II type 1 receptor during aging were accompanied by the generation of reactive species. Increased Ang II activated NF-kappaB by phosphorylating IkappaBalpha and p65. Increased phosphorylation of p65 at Ser 536 was mediated by the enhanced phosphorylation of IkappaB kinase alphabeta, while phosphorylation site Ser 276 of p65 was mediated by upregulated mitogen-activated and stress-activated protein kinase-1. These altered molecular events in aged animals were partly verified by experiments using YPEN-1 cells. Collectively, our findings provide molecular insights into the pro-inflammatory actions of Ang II, actions that influence the phosphorylation of p65-mediated NF-kappaB activation during aging. Our study demonstrates the age-related pleiotropic nature of the physiologically important Ang II can change into a deleterious culprit that contributes to an increased incidence of many chronic diseases such as atherosclerosis, diabetes, and dementia.

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CRRD Object Information
CRRD ID: 5129178
Created: 2011-03-25
Species: All species
Last Modified: 2011-03-25
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.