Proximal tubule dysfunction in cystine loaded tubules: effect of
phosphate and metabolic substrates.
Bajaj, Geeta, and Michel Baum.
Departments of Pediatrics and Internal Medicine, University of
Texas Southwestern Medical Center at Dallas, Dallas, Texas 75235
-9063
APStracts 3:0097F, 1996.
Intracellular cystine loading using cystine dimethyl ester results in
a generalized inhibition in proximal tubule transport due, in part,
to a decrease in intracellular ATP. The present study examined the
importance of phosphate and metabolic substrates in the proximal
tubule dysfunction produced by cystine loading. Proximal tubule
intracellular phosphorus was 1.8+/-0.1 in control tubules and 1.1+/
-0.1 nmol/mg protein in proximal tubules incubated in vitro with
cystine dimethyl ester (p<0.001). Infusion of sodium phosphate
in rabbits and subsequent incubation of proximal tubules with a high
phosphate media attenuated the decrease in proximal tubule
respiration and prevented the decrease in intracellular ATP upon
cystine loading. Tricarboxylic acid cycle intermediates have been
shown to preserve oxidative metabolism in phosphate depleted proximal
tubules. In proximal tubules incubated with either 1 mM valerate or
butyrate, there was a 42% and 34% reduction (both p<0.05) in the
rate of oxygen consumption upon cystine loading. However, tubules
incubated with 1 mM succinate or citrate had only a 13% and 14%
(p=NS) reduction in the rate of oxygen consumption, respectively.
These data are consistent with a limitation of intracellular
phosphate in the pathogenesis of the proximal tubule dysfunction with
cystine loading.
Received 23 October 1995; accepted in final form 2 May 1996.
APS Manuscript Number F358-5.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 5 June 96