AJP - Renal Physiology, Vol 271, Issue 3 717-F722, Copyright © 1996 by American Physiological Society
Proximal tubule dysfunction in cystine-loaded tubules: effect of phosphate and metabolic substrates
G. Bajaj and M. Baum
Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas 75235-9063, USA.
Intracellular cystine loading by use of cystine dimethyl ester (CDME)
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 CDME P < 0.001).
Infusion of sodium phosphate in rabbits and subsequent incubation of
proximal tubules with a high-phosphate medium attenuated the decrease in
proximal tubule respiration and prevented the decrease in intracellular ATP
with 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 with 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.
