Sepsis Increases Lung Glutamine Synthetase Expression in the Tumor-Bearing Host

• Published in: The Journal of surgical research Vol. 78; no. 1; pp. 18 - 22
• Main Authors: Elgadi, Khaled M., Labow, Brian I., Abcouwer, Steve F., Souba, Wiley W.
• Format: Journal Article Conference Proceeding
• Language: English
• Published: New York, NY Elsevier Inc 15.07.1998; Elsevier
• Subjects: Animal tumors. Experimental tumors; Animals; Biological and medical sciences; Blotting, Western; cachexia; Cachexia - metabolism; Experimental bone, joint and muscle tumors; Fibrosarcoma - metabolism; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; Glutamate-Ammonia Ligase - analysis; Glutamate-Ammonia Ligase - genetics; glutamine; Glutamine - metabolism; Lipopolysaccharides - pharmacology; lung; Lung - enzymology; Male; Medical sciences; muscle; Muscle Neoplasms - metabolism; Muscle, Skeletal - enzymology; Rats; Rats, Inbred F344; RNA, Messenger - analysis; Sepsis - metabolism; Tumors; lung; glutamine; muscle; cachexia; Rat; Lung; Fibrosarcoma; Synthase; Sepsis syndrome; Gene; Genetics; Complication; Muscle; Dietetics; Pathophysiology; Sarcoma; Enzyme; Rodentia; Cachexia; Malignant tumor; Experimental study; Gene expression; Infection; Vertebrata; Concomitant disease; Mammalia; Aminoacid; Animal; Molecular biology; Glutamine
• ISSN: 0022-4804; 1095-8673
• DOI: 10.1006/jsre.1998.5384

Acute stresses such as trauma or endotoxemia augment GLN demand and are associated with increased release of this amino acid from skeletal muscle and lung as well as increased expression of glutamine synthetase (GS, the principal enzyme of GLN synthesis) in these tissues. Muscle GLN release is also increased during chronic catabolic states which are associated with depletion of lean body mass, such as starvation or malignancy. We hypothesized that the expression of GS in response to an acute stress would be altered in tumor-bearing rats (TBR) experiencing severe cachexia and therefore a previously heightened GLN demand. Male Fischer 344 rats were implanted with methylcholanthrene-induced fibrosarcoma tumors or underwent sham operations and pair-feeding (sham) with TBR partners. When tumor burden reached approximately 15% of carcass weight, animals received injections of eitherEscherichia colilipopolysaccharide (LPS, 1 mg/kg body wt) or saline vehicle. Rats were sacrificed 8 h after injection and lung and muscle tissue were analyzed for GS mRNA and protein via Northern and Western blot techniques, respectively. LPS injection caused an equivalent 4- to 6-fold increase in lung and muscle GS mRNA in both TBR and sham rats (P< 0.01). LPS did not produce a significant increase in GS protein level in muscle tissue of either group or in lung tissue of sham rats. In contrast, endotoxin did lead to a 3.5-fold increase in GS protein levels in lung tissue of TBRs (P< 0.05). This increase in lung GS protein may signify the importance of the lung in maintaining GLN homeostasis during chronic catabolic states where muscle mass is diminished.