Pacitti A J, Inoue Y, Souba W W
Department of Surgery, University of Florida, Gainesville 32610.
J Clin Invest. 1993 Feb;91(2):474-83. doi: 10.1172/JCI116225.
Severe infection is characterized by a translocation of amino acids from the periphery to the liver, an event that is mediated in part by cytokines such as tumor necrosis factor-alpha (TNF). We investigated the activities of Na(+)-dependent transport systems A, ASC, and N in hepatic plasma membrane vesicles (HPMVs) prepared from rats treated with TNF in vivo. TNF did not alter sodium uptake but resulted in time- and dose-dependent fivefold and 50% maximal increases in system A and system N activity, respectively, in HPMVs secondary to an increase in the transport Vmax. Maximal increases in transport were observed 4 h after exposure to TNF and had returned to basal levels within 24 h. Similarly, system ASC activity was stimulated 80% in HPMVs from rats treated with TNF. Incubation of HPMVs from normal rats in vitro with TNF did not alter transport activity. Pretreatment of animals with the glucocorticoid receptor antagonist RU 38486 attenuated the TNF-induced enhancement in transport activity by 50%. The marked increase in Na(+)-dependent amino acid transport activity by TNF is mediated in part by the glucocorticoid hormones and represents an important mechanism underlying the accelerated hepatic amino acid uptake that occurs during critical illness.
严重感染的特征是氨基酸从外周向肝脏的转运，这一过程部分由细胞因子如肿瘤坏死因子-α（TNF）介导。我们研究了从体内用TNF处理的大鼠制备的肝细胞膜囊泡（HPMV）中Na(+)-依赖性转运系统A、ASC和N的活性。TNF不会改变钠摄取，但会导致HPMV中系统A和系统N的活性分别出现时间和剂量依赖性的五倍和50%的最大增加，这是由于转运Vmax增加所致。暴露于TNF后4小时观察到转运的最大增加，并在24小时内恢复到基础水平。同样，用TNF处理的大鼠的HPMV中系统ASC活性被刺激了80%。用糖皮质激素受体拮抗剂RU 38486对动物进行预处理可使TNF诱导的转运活性增强减弱50%。TNF引起的Na(+)-依赖性氨基酸转运活性的显著增加部分由糖皮质激素介导，是危重病期间肝脏氨基酸摄取加速的重要机制。
