Document Detail

Effects of endotoxin challenge on hepatic amino acid transport during cancer.
MedLine Citation:
PMID:  9698528     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: The hepatic uptake of amino acids is increased in both sepsis and cancer, and this response appears to be both global and essential in the catabolic host. Because immunocompromised cancer patients are susceptible to episodes of gram-negative sepsis, we examined the capacity of hepatocytes from normal and tumor-influenced livers to respond to the additional challenge of endotoxemia via increases in the Na+-dependent uptake of glutamine and zwitterionic amino acids by System N and System A, respectively. MATERIALS AND METHODS: Fischer 344 rats were implanted with methylcholanthrene-induced fibrosarcomas. Control rats were sham-operated and pair-fed. Animal pairs (tumor burden = 8-32% carcass weight) were injected intraperitoneally with either Escherichia coli endotoxin (10 mg/kg) or PBS, and after 4 h, hepatocytes were isolated from the livers of the animals via collagenase perfusion and placed in primary culture. Three hours later, amino acid transport rates were measured using radiolabeled glutamine for System N and alpha-methylaminoisobutyric acid (MeAIB), a nonmetabolizable substrate specific for System A. RESULTS: Cancer-independent of tumor size-and endotoxin each elicited similar 1.5- to 2-fold inductions of System N activity. When combined, their effects were additive rather than synergistic. In contrast, endotoxin induced an insignificant increase in System A activity, whereas cancer stimulated this carrier 2-fold in either the absence or the presence of endotoxin. CONCLUSIONS: The primary glutamine and alanine carriers in hepatocytes are differentially influenced during catabolic states, and the tumor-influenced liver is competent to further increase glutamine uptake in response to additional catabolic insults.
A M Easson; B P Bode; C P Fischer; W W Souba
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of surgical research     Volume:  77     ISSN:  0022-4804     ISO Abbreviation:  J. Surg. Res.     Publication Date:  1998 Jun 
Date Detail:
Created Date:  1998-09-04     Completed Date:  1998-09-04     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0376340     Medline TA:  J Surg Res     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  29-34     Citation Subset:  IM    
Copyright Information:
Copyright 1998 Academic Press.
Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, 02114, USA.
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MeSH Terms
Amino Acids / metabolism*
Biological Transport / drug effects
Endotoxins / blood,  pharmacology*
Fibrosarcoma / chemically induced,  metabolism*
Glutamine / metabolism
Lipopolysaccharides / pharmacology
Liver / metabolism*
Rats, Inbred F344
Reference Values
beta-Alanine / analogs & derivatives,  metabolism
Grant Support
Reg. No./Substance:
0/Amino Acids; 0/Endotoxins; 0/Lipopolysaccharides; 107-95-9/beta-Alanine; 19036-43-2/2,2-dimethyl-beta-alanine; 56-49-5/Methylcholanthrene; 56-85-9/Glutamine

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