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01.04.2006 | Original Article

Glutathione depletion and increased apoptosis rate in human cystinotic proximal tubular cells

verfasst von: Guido F. Laube, Vanita Shah, Victoria C. Stewart, Iain P. Hargreaves, Mushfequr R. Haq, Simon J. R. Heales, William G. van’t Hoff

Erschienen in: Pediatric Nephrology | Ausgabe 4/2006

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Abstract

We have determined levels of glutathione (GSH), ATP, mitochondrial complex activity and apoptosis rate in proximal tubular cells (PTCs) exfoliated from urine in cystinotic (n=9) and control (n=9) children. Intracellular GSH was significantly depleted in cystinotic PTCs compared with controls (6.8 nmol GSH/mg protein vs 11.8 nmol GSH/mg protein; P<0.001), but there were no significant differences in mitochondrial complex activities or ATP levels under basal conditions. Cystinotic PTCs showed significantly increased apoptosis rate. After PTCs had been stressed by hypoxia, there was further depletion of GSH in cystinotic and control PTCs (2.4 nmol GSH/mg protein vs 7.2 nmol GSH/mg protein; P<0.001). Hypoxic stress led to increased complex I and complex IV activities in control but not in cystinotic PTCs. ATP levels were significantly reduced in cystinotic PTCs after hypoxic stress (12.2 nmol/mg protein vs 26.9 nmol/mg protein; P<0.001). GSH depletion occurs in this in vitro model of cystinotic PTCs, is exaggerated by hypoxic stress and may contribute to reduced ATP and failure to increase complex I/IV activities. Apoptotic rate is also increased, and these mechanisms may contribute to cellular dysfunction in cultured, human cystinotic PTCs.

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Titel: Glutathione depletion and increased apoptosis rate in human cystinotic proximal tubular cells
verfasst von: Guido F. Laube
Vanita Shah
Victoria C. Stewart
Iain P. Hargreaves
Mushfequr R. Haq
Simon J. R. Heales
William G. van’t Hoff
Publikationsdatum: 01.04.2006
Verlag: Springer-Verlag
Erschienen in: Pediatric Nephrology / Ausgabe 4/2006
Print ISSN: 0931-041X
Elektronische ISSN: 1432-198X
DOI: https://doi.org/10.1007/s00467-006-0005-x

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Glutathione depletion and increased apoptosis rate in human cystinotic proximal tubular cells

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