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

Percy, C. J. and Brown, Lindsay and Power, D. A. and Johnson, David W. and Gobe, Glenda C. (2009) Obesity and hypertension have differing oxidant handling molecular pathways in age-related chronic kidney disease. Mechanisms of Ageing and Development, 130 (3). pp. 129-138. ISSN 0047-6374


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.

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Item Type: Article (Commonwealth Reporting Category C)
Refereed: Yes
Item Status: Live Archive
Additional Information: Permanent restricted access to published version due to publisher copyright policy.
Faculty / Department / School: Historic - Faculty of Sciences - Department of Biological and Physical Sciences
Date Deposited: 30 Aug 2011 23:49
Last Modified: 26 Jul 2014 00:06
Uncontrolled Keywords: ageing; AMPK; fibrosis; FoxO1; oxidative stress; p66Shc
Fields of Research : 11 Medical and Health Sciences > 1103 Clinical Sciences > 110312 Nephrology and Urology
11 Medical and Health Sciences > 1101 Medical Biochemistry and Metabolomics > 110107 Metabolic Medicine
10 Technology > 1004 Medical Biotechnology > 100401 Gene and Molecular Therapy
Socio-Economic Objective: C Society > 92 Health > 9205 Specific Population Health (excl. Indigenous Health) > 920502 Health Related to Ageing
Identification Number or DOI: 10.1016/j.mad.2008.10.003
URI: http://eprints.usq.edu.au/id/eprint/19364

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