Hepatic glutamine transporter activation in burn injury: role of amino acids and phosphatidylinositol-3-kinase

被引:8
作者
Pawlik, TM
Lohmann, R
Souba, WW
Bode, BP
机构
[1] Massachusetts Gen Hosp, Dept Surg, Surg Oncol Res Labs, Boston, MA 02114 USA
[2] Harvard Univ, Sch Med, Boston, MA 02114 USA
来源
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY | 2000年 / 278卷 / 04期
关键词
liver; glucagon; cell volume; signal transduction;
D O I
10.1152/ajpgi.2000.278.4.G532
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Burn injury elicits a marked, sustained hypermetabolic state in patients characterized by accelerated hepatic amino acid metabolism and negative nitrogen balance. The transport of glutamine, a hey substrate in gluconeogenesis and ureagenesis, was examined in hepatocytes isolated from the livers of rats after a 20% total burn surface area full-thickness scald injury. A latent and profound two- to threefold increase in glutamine transporter system N activity was first observed after 48 h in hepatocytes from injured rats compared with controls, persisted for 9 days, and waned toward control values after 18 Bays, corresponding with convalescence. Further studies showed that the profound increase was fully attributable to rapid posttranslational transporter activation by amino acid-induced cell swelling and that this form of regulation may be elicited in part by glucagon. The phosphatidylinositol-3-kinase (PI3K) inhibitors wortmannin and LY-294002 each significantly attenuated transporter stimulation by amino acids. The data suggest that PI3K-dependent system N activation by amino acids may play an important role in fueling accelerated hepatic nitrogen metabolism after burn injury.
引用
收藏
页码:G532 / G541
页数:10
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