Bajaj G, Baum M
Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas 75235-9063, USA.
Am J Physiol. 1996 Sep;271(3 Pt 2):F717-22. doi: 10.1152/ajprenal.1996.271.3.F717.
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.
使用胱氨酸二甲酯（CDME）进行细胞内胱氨酸加载会导致近端小管转运普遍受到抑制，部分原因是细胞内ATP减少。本研究探讨了磷酸盐和代谢底物在胱氨酸加载所致近端小管功能障碍中的重要性。对照小管近端小管细胞内磷为1.8±0.1，在体外与CDME一起孵育的近端小管中为1.1±0.1 nmol/mg蛋白质（P<0.001）。给兔子输注磷酸钠，随后将近端小管与高磷培养基一起孵育，可减轻近端小管呼吸的下降，并防止胱氨酸加载时细胞内ATP的减少。三羧酸循环中间产物已被证明可维持磷酸盐缺乏的近端小管中的氧化代谢。在用1 mM戊酸盐或丁酸盐孵育的近端小管中，胱氨酸加载时耗氧率分别降低了42%和34%（均P<0.05）。然而，用1 mM琥珀酸盐或柠檬酸盐孵育的小管耗氧率仅分别降低了13%和14%（P=无显著性差异）。这些数据与细胞内磷酸盐在胱氨酸加载所致近端小管功能障碍发病机制中的限制作用一致。
