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
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.
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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/School / Institute/Centre: | Historic - Faculty of Sciences - Department of Biological and Physical Sciences (Up to 30 Jun 2013) |
| Faculty/School / Institute/Centre: | Historic - Faculty of Sciences - Department of Biological and Physical Sciences (Up to 30 Jun 2013) |
| 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 (2008): | 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 Objectives (2008): | C Society > 92 Health > 9205 Specific Population Health (excl. Indigenous Health) > 920502 Health Related to Ageing |
| Identification Number or DOI: | https://doi.org/10.1016/j.mad.2008.10.003 |
| URI: | http://eprints.usq.edu.au/id/eprint/19364 |
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