title: Sodium-pump gene-expression, protein abundance and enzyme activity in isolated nephron segments of the aging rat kidney.
abstract: Aging is associated with alteration in renal tubular functions, including sodium handling and concentrating ability. Na-K-ATPase plays a key role in driving tubular transport, and we hypothesized that decreased concentrating ability of the aging kidney is due in part to downregulation of Na-K-ATPase. In this study, we evaluated Na and K balance, aldosterone levels, and Na-K-ATPase gene expression, protein abundance, and activity in aging rat kidney. Na-K-ATPase activity (assayed microfluorometrically), mRNA (RT-PCR), and protein abundance (immunoblotting) were quantitated in the following isolated nephron segments: PCT, PST, MTAL, DCT, and CCD from 2, 8, 15, and 24 month-old-rats. In the course of aging, creatinine clearance decreased from 0.48 ± 0.02 mL/min/100 g BW to 0.28 ± 0.06 (P < 0.001) and aldosterone decreased from 23.6 ± 0.8 ng/dL to 13.2 ± 0.6 (P < 0.001). Serum Na(+) and K(+) increased by 4.0% and 22.5%, respectively. Na-K-ATPase activity, mRNA, and protein abundance of the α1 subunit displayed similar trends in all assayed segments; increasing in PCT and PST; decreasing in MTAL and DCT; increasing in CCD: in PCT they increased by 40%, 75%, and 250%, respectively; while in PST they increased by 80%, 50%, and 100%, respectively (P < 0.001). In MTAL they declined by 36%, 24%, and 34%, respectively, and in DCT by 38%, 59%, and 60%, respectively (P < 0.001). They were higher in CCD by 110%, 115%, and 246%, respectively (P < 0.001). Rats maintained Na/K balance; however with a steady state elevated serum K(+). These results reveal quantitative changes in axial distribution of Na-K-ATPase at the level of gene expression, protein abundance, and activity in the nephrons of aging animals and may explain, in part, the pathophysiology of the senescent kidney.
authors.affiliation: Nephrology and Hypertension Services, Hadassah University Hospital, Jerusalem, Israel spnina@hadassah.org.il.
authors.forename: Pnina
authors.initials: P
authors.lastname: Scherzer
authors.affiliation: Nephrology and Hypertension Services, Hadassah University Hospital, Jerusalem, Israel.
authors.forename: Anca
authors.initials: A
authors.lastname: Gal-Moscovici
authors.affiliation: Nephrology and Hypertension Services, Hadassah University Hospital, Jerusalem, Israel Nephrology Division, Department of Medicine, Baylor College of Medicine, Houston, Texas.
authors.forename: David
authors.initials: D
authors.lastname: Sheikh-Hamad
authors.affiliation: Nephrology and Hypertension Services, Hadassah University Hospital, Jerusalem, Israel South Arizona VA Health Care System and University of Arizona, Tucson, Arizona.
authors.forename: Mordecai M
authors.initials: MM
authors.lastname: Popovtzer
keywords: Aldosterone; Na+‐K+‐ ATPase; dissected tubules; senescent rats