Tannen R L, Sahai A
Department of Medicine, University of Southern California, Los Angeles.
Am J Kidney Dis. 1989 Oct;14(4):281-4. doi: 10.1016/s0272-6386(89)80203-3.
LLC-PK1 kidney epithelial cell lines cultured under the condition of continuous rocking exhibit both acute and adaptive changes in glutamine-dependent ammonia metabolism in response to acid-base manipulations in the media pH. Pulse-chase studies with 14C-glutamine as well as studies with various metabolic inhibitors of the ammoniagenic pathways suggest that glutamine in LLC-PK1 cells is metabolized via mitochondrial pathway and that intramitochondrial phosphate-dependent glutaminase pathway plays a predominant role in the regulation of ammoniagenesis to acute acidosis. Furthermore, the measurements of intracellular pH under both basal and acute low pH conditions resulted in the estimation of intracellular pH, which paralleled the alterations in media pH. Therefore, a change in intracellular pH appears to act as a direct signal for alterations in ammonia metabolism in LLC-PK1 cells. Thus, LLC-PK1 cultures provide an excellent model system to investigate renal ammoniagenesis and the intracellular signals that modulate this process.
在持续摇晃条件下培养的LLC-PK1肾上皮细胞系，在培养基pH值进行酸碱调控时，谷氨酰胺依赖性氨代谢会出现急性和适应性变化。用14C-谷氨酰胺进行的脉冲追踪研究以及对氨生成途径的各种代谢抑制剂的研究表明，LLC-PK1细胞中的谷氨酰胺通过线粒体途径代谢，并且线粒体内磷酸盐依赖性谷氨酰胺酶途径在急性酸中毒时氨生成的调节中起主要作用。此外，在基础和急性低pH条件下对细胞内pH的测量得出了细胞内pH的估计值，该值与培养基pH的变化平行。因此，细胞内pH的变化似乎是LLC-PK1细胞中氨代谢改变的直接信号。因此，LLC-PK1培养物提供了一个极好的模型系统，用于研究肾氨生成以及调节这一过程的细胞内信号。
