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


Laube, Guido F; Shah, Vanita; Stewart, Victoria C; Hargreaves, Iain P; Haq, Mushfequr R; Heales, Simon J R; van't Hoff, William G (2006). Glutathione depletion and increased apoptosis rate in human cystinotic proximal tubular cells. Pediatric Nephrology, 21(4):503-509.

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 (6.8nmol GSH/mg protein vs 11.8nmol 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 (2.4nmol GSH/mg protein vs 7.2nmol GSH/mg protein; P<0.001). Hypoxic stress led to increased complexI and complexIV activities in control but not in cystinotic PTCs. ATP levels were significantly reduced in cystinotic PTCs after hypoxic stress (12.2nmol/mg protein vs 26.9nmol/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 complexI/IV activities. Apoptotic rate is also increased, and these mechanisms may contribute to cellular dysfunction in cultured, human cystinotic PTCs

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 (6.8nmol GSH/mg protein vs 11.8nmol 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 (2.4nmol GSH/mg protein vs 7.2nmol GSH/mg protein; P<0.001). Hypoxic stress led to increased complexI and complexIV activities in control but not in cystinotic PTCs. ATP levels were significantly reduced in cystinotic PTCs after hypoxic stress (12.2nmol/mg protein vs 26.9nmol/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 complexI/IV activities. Apoptotic rate is also increased, and these mechanisms may contribute to cellular dysfunction in cultured, human cystinotic PTCs

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Item Type:Journal Article, refereed, original work
Communities & Collections:National licences > 142-005
Dewey Decimal Classification:610 Medicine & health
Scopus Subject Areas:Health Sciences > Pediatrics, Perinatology and Child Health
Health Sciences > Nephrology
Language:English
Date:1 April 2006
Deposited On:03 Jul 2019 12:25
Last Modified:31 Jul 2020 02:49
Publisher:Springer
ISSN:0931-041X
OA Status:Green
Publisher DOI:https://doi.org/10.1007/s00467-006-0005-x
Related URLs:https://www.swissbib.ch/Search/Results?lookfor=nationallicencespringer101007s004670060005x (Library Catalogue)
PubMed ID:16508773

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