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-kappaB, 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-kappaB 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.
Publication types
-
Comparative Study
-
Research Support, Non-U.S. Gov't
MeSH terms
-
AMP-Activated Protein Kinases / metabolism
-
Adiposity
-
Age Factors
-
Aging / metabolism*
-
Animals
-
Autophagy
-
Body Weight
-
Chronic Disease
-
Disease Models, Animal
-
Extracellular Signal-Regulated MAP Kinases / metabolism
-
Fibrosis
-
Forkhead Transcription Factors / metabolism
-
Heme Oxygenase (Decyclizing) / metabolism
-
Hypertension / metabolism*
-
Hypertension / pathology
-
Hypertension / physiopathology
-
Kidney / metabolism*
-
Kidney / pathology
-
Kidney / physiopathology
-
Kidney Diseases / metabolism*
-
Kidney Diseases / pathology
-
Kidney Diseases / physiopathology
-
L-Lactate Dehydrogenase / blood
-
Male
-
NF-kappa B / metabolism
-
Nerve Tissue Proteins / metabolism
-
Obesity / metabolism*
-
Obesity / pathology
-
Obesity / physiopathology
-
Oxidants / metabolism*
-
Oxidative Stress*
-
Phosphorylation
-
Proto-Oncogene Proteins c-akt / metabolism
-
Proto-Oncogene Proteins c-bcl-2 / metabolism
-
Rats
-
Rats, Inbred SHR
-
Rats, Inbred WKY
-
Shc Signaling Adaptor Proteins / metabolism
-
Signal Transduction
-
Src Homology 2 Domain-Containing, Transforming Protein 1
-
bcl-2-Associated X Protein / metabolism
Substances
-
Bax protein, rat
-
Forkhead Transcription Factors
-
NF-kappa B
-
Nerve Tissue Proteins
-
Oxidants
-
Proto-Oncogene Proteins c-bcl-2
-
Shc Signaling Adaptor Proteins
-
Shc1 protein, rat
-
Src Homology 2 Domain-Containing, Transforming Protein 1
-
bcl-2-Associated X Protein
-
Foxo1 protein, rat
-
L-Lactate Dehydrogenase
-
Heme Oxygenase (Decyclizing)
-
Hmox1 protein, rat
-
Proto-Oncogene Proteins c-akt
-
Extracellular Signal-Regulated MAP Kinases
-
AMP-Activated Protein Kinases