Renal cytoplasmic proteasome proteinase activities are altered in chronic renal failure.
The effect of uremia on renal cortex cytoplasmic proteasomes was examined by comparing proteasomes isolated from 5/6th nephrectomy rats 3-months post-surgery and age-matched control rats with normal renal function. ATP-dependent proteasome activity was reduced 50% in chronic renal failure rats (CRF) 3-months post-surgery compared to age-matched control rats. Trypsin-like (T-like) proteasome activity was decreased 90% compared to 70% for caspase-like activity (PGPHase) and 30% for chymotrypsin-like activity (C-like). ATP-independent proteasome activity was decreased 60% in CRF rats 3-months post-surgery. ATP-independent renal cortex proteasome T-like activity in CRF rats was 4% of age-matched control rats. C-like and PGPHase activities were 60% and 50% of age-matched controls, respectively. Uremia was associated with decreased 26S proteasome beta subunits. CRF rat 26S proteasomes had decreased levels of beta1, beta3, alpha4, and alpha7 abundances. Compared to age-matched control rats with normal renal function, CRF rats had a 25% increase in ubiquitinated cytoplasmic proteins. Decreased renal cytoplasmic proteasome activity may play a role in renal tubule hypertrophy common to renal diseases associated with decreased functioning nephrons.
Peerce
Brian E
BE
Department of Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, 77555-0641, USA. bpeerce@utmb.edu
Clarke
Rebecca D
RD
D000818:Animals; D003593:Cytoplasm / Q000201:enzymology; D007672:Kidney Cortex / Q000201:enzymology*; D007676:Kidney Failure, Chronic / Q000201:enzymology* / Q000209:etiology; D009392:Nephrectomy / Q000009:adverse effects; D010447:Peptide Hydrolases / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D051381:Rats; D025801:Ubiquitin / Q000378:metabolism; D014511:Uremia / Q000201:enzymology* / Q000209:etiology
D025801:Ubiquitin; D010447:Peptide Hydrolases; D046988:Proteasome Endopeptidase Complex