TY - JOUR
T1 - Proximal tubule dysfunction in cystine-loaded tubules
T2 - Effect of phosphate and metabolic substrates
AU - Bajaj, Geeta
AU - Baum, Michel
PY - 1996
Y1 - 1996
N2 - Intracellular cys-tine 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 highphosphate 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.
AB - Intracellular cys-tine 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 highphosphate 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.
KW - Cystine dimethyl ester
KW - Cystinosis
KW - Fanconi syndrome
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U2 - 10.1152/ajprenal.1996.271.3.f717
DO - 10.1152/ajprenal.1996.271.3.f717
M3 - Article
C2 - 8853435
AN - SCOPUS:0029797673
SN - 0002-9513
VL - 271
SP - F717-F722
JO - American Journal of Physiology
JF - American Journal of Physiology
IS - 3 PART 2
ER -