Obesity and hypertension have differing oxidant handling molecular pathways in age-related chronic kidney disease
Article
Article Title | Obesity and hypertension have differing oxidant handling molecular pathways in age-related chronic kidney disease |
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ERA Journal ID | 16583 |
Article Category | Article |
Authors | Percy, C. J. (Author), Brown, Lindsay (Author), Power, D. A. (Author), Johnson, David W. (Author) and Gobe, Glenda C. (Author) |
Journal Title | Mechanisms of Ageing and Development |
Journal Citation | 130 (3), pp. 129-138 |
Number of Pages | 10 |
Year | 2009 |
Place of Publication | Shannon, Co. Clare, Ireland |
ISSN | 0047-6374 |
1872-6216 | |
Digital Object Identifier (DOI) | https://doi.org/10.1016/j.mad.2008.10.003 |
Web Address (URL) | http://www.sciencedirect.com/science/article/pii/S0047637408001899 |
Abstract | Chronic kidney disease (CKD) in ageing is a burden on health systems worldwide. Rat models of age-related CKD linked with obesity and hypertension were used to investigate alterations in oxidant handling and energy metabolism to identify gene targets or markers for age-related CKD. Young adult (3 months) and old (21-24 months) spontaneously-hypertensive (SHR), normotensive Wistar-Kyoto (WKY) and Wistar rats (normotensive, obese in ageing) were compared for renal functional and physiological parameters, renal fibrosis and inflammation, oxidative stress (hemeoxygenase-1/HO-1), apoptosis and cell injury (including Bax:Bcl-2), phosphorylated and non-phosphorylated forms of oxidant and energy sensing proteins (p66Shc, AMPK), signal transduction proteins (ERK1/2, PKB), and transcription factors (NF-κB, FoxO1). All old rats were normoglycemic. Renal fibrosis, tubular epithelial apoptosis, interstitial macrophages and myofibroblasts (all p < 0.05), p66Shc/phospho-p66 (p < 0.05), Bax/Bcl-2 ratio (p < 0.05) and NF-κB expression (p < 0.01) were highest in old obese Wistars. Expression of phospho-FoxO/FoxO was elevated in old Wistars (p < 0.001) and WKYs (p < 0.01). SHRs had high levels in young and old rats. Expression of PKB, phospho-PKB, ERK1/2 and phospho-ERK1/2 were significantly elevated in all aged animals. These results suggest that obesity and hypertension have differing oxidant handling and signalling pathways that act in the pathogenesis of age-related CKD. |
Keywords | ageing; AMPK; fibrosis; FoxO1; oxidative stress; p66Shc |
ANZSRC Field of Research 2020 | 320214. Nephrology and urology |
320507. Metabolic medicine | |
320601. Gene and molecular therapy | |
Public Notes | Files associated with this item cannot be displayed due to copyright restrictions. |
Byline Affiliations | University of Queensland |
Department of Health, Victoria | |
Department of Health, Queensland | |
Institution of Origin | University of Southern Queensland |
https://research.usq.edu.au/item/q0w3y/obesity-and-hypertension-have-differing-oxidant-handling-molecular-pathways-in-age-related-chronic-kidney-disease
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