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Abnormal glyceraldehyde-3-phosphate dehydrogenase binding and glycolytic flux in Autosomal Dominant Polycystic Kidney Disease after a mild oxidative stress

Lookup NU author(s): Dr Trevor Thomas, Dr Ian West

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Abstract

Aim:The aim of this study was, a) to investigate the effect of mild oxidative stress on glycolytic fux and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) binding in erythrocytes from patients with autosomal dominant polycystic kidney disease (ADPKD), and b) to examine whether the modulation of GAPDH-binding to the red cell membrane leads to changes in glycolytic fux. Patients and methods: The rate of lactate production in intact erythrocytes and the GAPDH/actin ratio in erythrocyte ghost membranes were measured before and after treating cells with t-butyl hydroperoxide or N-ethylmaleimide (NEM) in 13 ADPKD patients and 12 controls. Results: t-bytyl hydro-peroxide had a signifcant effect on both lactate production and GAPDH/actin ratio in healthy subjects, but it had essentially no effect on ADPKD patients in which both parameters already resembled those of the peroxide-treated controls. NEM treatment after 300 sec had a very signifcant effect on both lactate production and GAPDH/actin ratio in both patient and control cells. However, after 10 sec the effect on GAPDH/actin ratio was only signifcant in the erythrocytes of ADPKD patients. In every experiment glycolytic lactate production correlated negatively with membrane-bound GAPDH/actin ratio. Conclusions: We conclude that glycolytic fux and GAPDH binding in erythrocytes from ADPKD patients respond abnormally to both a mild oxidative stress and brief exposure to NEM.


Publication metadata

Author(s): Dioudis C, Grekas D, Thomas TH, West IC

Publication type: Article

Publication status: Published

Journal: Hippokratia

Year: 2008

Volume: 12

Issue: 3

Pages: 162-167

Print publication date: 01/01/2008

ISSN (print): 1108-4189

ISSN (electronic):

Publisher: Hippokratio General Hospital of Thessaloniki

URL: http://www.hippokratia.gr/index.php/hippo/article/view/622


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