Regulation of glucose transport by tumor necrosis factor-alpha in cultured murine 3T3-L1 fibroblasts.
We have examined the ability of tumor necrosis factor-alpha (TNF) to stimulate hexose transport in 3T3-L1 fibroblasts. Activation of transport occurred in a dose- and time-dependent manner, with maximal stimulation (fourfold) occurring approximately 15 hours after exposure to 2.5 nM TNF. The protein synthesis inhibitor, cycloheximide, blunted TNF-induced 2-deoxyglucose uptake, suggesting that new synthesis was in part responsible for the observed increase. Increased hexose transport occurred concomitant with a 50% increase in general protein synthesis which preceded a fivefold stimulation of thymidine incorporation into DNA. Elevated hexose transport preceded an accumulation of glucose transporter (GLUT-1) mRNA. We have further demonstrated that the early accumulation of GLUT-1 mRNA is accompanied by accumulation of mRNA for both the prootooncogene c-fos as well as that for beta-actin. We suggest that these events represent the pleiotrophic growth factor-like properties of TNF-alpha.
Cornelius
P
P
Department of Biochemistry, East Carolina University, Greenville, NC 27858.
Marlowe
M
M
Pekala
P H
PH
D000199:Actins / Q000235:genetics; D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D004261:DNA Replication; D003847:Deoxyglucose / Q000378:metabolism / Q000493:pharmacokinetics; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D005947:Glucose / Q000378:metabolism / Q000493:pharmacokinetics*; D007930:Leucine / Q000378:metabolism / Q000493:pharmacokinetics; D051379:Mice; D009004:Monosaccharide Transport Proteins / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger / Q000032:analysis; D013936:Thymidine / Q000378:metabolism / Q000493:pharmacokinetics; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D000199:Actins; D009004:Monosaccharide Transport Proteins; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D003513:Cycloheximide; D003847:Deoxyglucose; D007930:Leucine; D005947:Glucose; D013936:Thymidine