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., & 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), pp. 129-138.

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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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ID Code: 78060
Item Type: Journal Article
Refereed: Yes
Keywords: oxidative stress, p66Shc, AMPK, Fox01, Fibrosis, aging
DOI: 10.1016/j.mad.2008.10.003
ISSN: 0047-6374
Subjects: Australian and New Zealand Standard Research Classification > BIOLOGICAL SCIENCES (060000) > OTHER BIOLOGICAL SCIENCES (069900)
Divisions: Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Deposited On: 27 Oct 2014 03:11
Last Modified: 28 Oct 2014 00:20

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