Obesity and hypertension have differing oxidant handling molecular pathways in age-related chronic kidney disease

Percy, C. J., Brown, L., Power, D. A., Johnson D. W. and Gobe, G. C. (2009) Obesity and hypertension have differing oxidant handling molecular pathways in age-related chronic kidney disease. Mechanisms of Ageing And Development, 130 3: 129-138. doi:10.1016/j.mad.2008.10.003


Author Percy, C. J.
Brown, L.
Power, D. A.
Johnson D. W.
Gobe, G. C.
Title Obesity and hypertension have differing oxidant handling molecular pathways in age-related chronic kidney disease
Journal name Mechanisms of Ageing And Development   Check publisher's open access policy
ISSN 0047-6374
Publication date 2009-01-01
Year available 2008
Sub-type Article (original research)
DOI 10.1016/j.mad.2008.10.003
Open Access Status
Volume 130
Issue 3
Start page 129
End page 138
Total pages 10
Editor V. A. Bohr
Place of publication Dublin, Ireland
Publisher Elsevier Ireland
Language eng
Subject C1
111501 Basic Pharmacology
920106 Endocrine Organs and Diseases (excl. Diabetes)
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 (herneoxygenase-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-kappa B, FoxO1). All old rats were normoglycemnic. 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-kappa B 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. (C) 2008 Elsevier Ireland Ltd. All rights reserved.
Keyword Oxidative stress
p66Shc
AMPK
Fox01
Fibrosis
Ageing
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

 
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Created: Fri, 17 Apr 2009, 21:01:29 EST by Shirley Rey on behalf of School of Biomedical Sciences