Tumor necrosis factor stimulates amino acid transport in plasma membrane vesicles from rat liver.
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.
Pacitti
A J
AJ
Department of Surgery, University of Florida, Gainesville 32610.
Inoue
Y
Y
Souba
W W
WW
D000596:Amino Acids / Q000378:metabolism*; D000621:Aminoisobutyric Acids / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D002462:Cell Membrane / Q000378:metabolism; D003545:Cysteine / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D015735:Mifepristone / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000378:metabolism / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D000596:Amino Acids; D000621:Aminoisobutyric Acids; D014409:Tumor Necrosis Factor-alpha; D005973:Glutamine; C017911:2-(methylamino)isobutyric acid; D015735:Mifepristone; D012964:Sodium; D003545:Cysteine