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Titolo:
Low Ca2+ pump activity in diabetic nephropathy
Autore:
Podesta, F; Meregalli, G; Ghelardi, R; Del Giudice, R; Asnaghi, V; Maestroni, A; Zerbini, G;
Indirizzi:
Univ Milan, San Raffaele Sci Inst, Div Med, Renal Pathophysiol Lab, I-20132 Milan, Italy Univ Milan Milan Italy I-20132 al Pathophysiol Lab, I-20132 Milan, Italy
Titolo Testata:
AMERICAN JOURNAL OF KIDNEY DISEASES
fascicolo: 3, volume: 38, anno: 2001,
pagine: 465 - 472
SICI:
0272-6386(200109)38:3<465:LCPAID>2.0.ZU;2-6
Fonte:
ISI
Lingua:
ENG
Soggetto:
NA+/H+ ANTIPORT ACTIVITY; SPONTANEOUSLY HYPERTENSIVE RAT; CULTURED SKIN FIBROBLASTS; SMOOTH-MUSCLE CELLS; SODIUM-PROTON EXCHANGE; INTRACELLULAR PH; GROWTH-FACTORS; IDDM PATIENTS; CALCIUM-PUMP; PLASMA-MEMBRANE;
Keywords:
insulin-dependent diabetes mellitus (IDDM); diabetic nephropathy (DN); Ca2+ pump; Na+-H+ exchange (NHE); human skin fibroblasts;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Citazioni:
49
Recensione:
Indirizzi per estratti:
Indirizzo: Zerbini, G Univ Milan, San Raffaele Sci Inst, Div Med 1, Via Olgettina 60,I-20132 Milan, Italy Univ Milan Via Olgettina 60 Milan Italy I-20132 2 Milan, Italy
Citazione:
F. Podesta et al., "Low Ca2+ pump activity in diabetic nephropathy", AM J KIDNEY, 38(3), 2001, pp. 465-472

Abstract

Elevated cell Na+-H+ exchange (NHE) activity characterizes diabetic nephropathy (DN), but the mechanisms of this abnormality are unclear. Recent evidence suggests that NHE and the Ca2+ pump share similar regulatory pathways,but whether abnormalities in Ca2+ metabolism characterize DN is not known. We investigated Ca2+ efflux rates, NHE activity, cytosolic Ca2+ ([Ca2+](i)) concentrations, and intracellular pH (pH(i)) in human skin fibroblasts from 20 patients with type 1 (insulin-dependent) diabetes and nephropathy; 20patients with diabetes with normoalbuminuria matched for age, sex, and duration of diabetes; and 10 individuals without diabetes. Ca2+ pump-mediated Ca2+ efflux was significantly lower in patients with nephropathy than in patients with normoalbuminuria and individuals without diabetes (0.074 +/- 0.01 versus 0.115 +/- 0.01 versus 0.131 +/- 0.02 nmol.mg(protein)(-1).min(-1); analysis of variance [ANOVA], P = 0.015). Elevated maximal velocity of the Na+-H+ exchanger was confirmed in fibroblasts from patients with nephropathy (14.4 +/- 1.2 versus 7.1 +/- 0.7 versus 8.0 +/- 1.2 mmol H+.l cell(-1).min(-1); ANOVA, P < 0.0001). A reverse correlation between Ca2+ pump activity and NHE rates could be shown. Adjustment for glycated hemoglobin and plasma lipid levels did not affect these findings. Finally, [Ca2+](i) concentrations and pH(i) were normal in all patients. Low Ca2+ pump activity is a concomitant event of elevated NHE rates in DN; the molecular dysfunction(s) underlying these abnormalities remains to be established. (C) 2001 by the National Kidney Foundation, Inc.

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Documento generato il 19/01/20 alle ore 11:43:20