Percy, Christine 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
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Identification Number or DOI: doi: 10.1016/j.mad.2008.10.003
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.
|Item Type:||Article (Commonwealth Reporting Category C)|
|Additional Information:||Permanent restricted access to published version due to publisher copyright policy.|
|Uncontrolled Keywords:||ageing; AMPK; fibrosis; FoxO1; oxidative stress; p66Shc|
|Fields of Research (FOR2008):||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 (SEO2008):||C Society > 92 Health > 9205 Specific Population Health (excl. Indigenous Health) > 920502 Health Related to Ageing|
|Deposited On:||31 Aug 2011 09:49|
|Last Modified:||24 Jan 2012 11:26|
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