PMID- 8663078
OWN - NLM
STAT- MEDLINE
DCOM- 19960813
LR  - 20210210
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 271
IP  - 25
DP  - 1996 Jun 21
TI  - Glucose metabolism to glucosamine is necessary for glucose stimulation of 
      transforming growth factor-alpha gene transcription.
PG  - 15237-43
AB  - Transforming growth factor-alpha (TGFalpha) gene transcription can be increased 
      when arterial smooth muscle cells are exposed to supraphysiological 
      concentrations of glucose, and this effect of glucose can be mimicked by 
      glucosamine. To determine whether the metabolism of glucose to glucosamine is 
      required for this glucose effect, the rate-limiting step in glucose metabolism to 
      glucosamine through the enzyme glutamine:fructose-6-phosphate amidotransferase 
      (GFAT) was blocked using pharmacological and antisense strategies. We found that 
      blockage of GFAT activity or expression significantly blunted the glucose-induced 
      increase of TGFalpha expression. Blockage of GFAT also resulted in a decreased 
      RL2 signal on intracellular proteins as detected by Western blotting and indirect 
      immunofluorescence. The RL2 monoclonal antibody recognizes an epitope on proteins 
      that contain N-acetylglucosamine and thus is a measure of protein glycosylation. 
      Conversely, treatment of the cells with glucose and glucosamine resulted in an 
      increase in the RL2 epitope on intracellular proteins. These results indicate 
      that the metabolism of glucose to glucosamine is necessary for the 
      transcriptional stimulation of TGFalpha expression in vascular smooth muscle 
      cells by glucose. Furthermore, the level of glycosylation of some intracellular 
      proteins can be modulated in response to physiological changes in the 
      extracellular glucose concentration and the net activity of GFAT.
FAU - Sayeski, P P
AU  - Sayeski PP
AD  - Department of Medicine, Division of Endocrinology and Metabolism, University of 
      Alabama at Birmingham, Birmingham, Alabama 35294, USA.
FAU - Kudlow, J E
AU  - Kudlow JE
LA  - eng
GR  - DK43652/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Transforming Growth Factor alpha)
RN  - 03J0H273KZ (Diazooxonorleucine)
RN  - EC 1.13.12.- (Luciferases)
RN  - EC 2.6.1.16 (Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing))
RN  - IY9XDZ35W2 (Glucose)
RN  - N08U5BOQ1K (Glucosamine)
SB  - IM
MH  - Animals
MH  - Antibodies, Monoclonal
MH  - Aorta
MH  - Cells, Cultured
MH  - Diazooxonorleucine/pharmacology
MH  - Fluorescent Antibody Technique, Indirect
MH  - Glucosamine/metabolism/*pharmacology
MH  - Glucose/metabolism/*pharmacology
MH  - Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing)/metabolism
MH  - Glycosylation
MH  - Kinetics
MH  - Luciferases/biosynthesis
MH  - Male
MH  - Muscle, Smooth, Vascular/*metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Recombinant Proteins/biosynthesis
MH  - *Transcription, Genetic/drug effects
MH  - Transforming Growth Factor alpha/*biosynthesis
EDAT- 1996/06/21 00:00
MHDA- 1996/06/21 00:01
CRDT- 1996/06/21 00:00
PHST- 1996/06/21 00:00 [pubmed]
PHST- 1996/06/21 00:01 [medline]
PHST- 1996/06/21 00:00 [entrez]
AID - S0021-9258(18)37311-3 [pii]
AID - 10.1074/jbc.271.25.15237 [doi]
PST - ppublish
SO  - J Biol Chem. 1996 Jun 21;271(25):15237-43. doi: 10.1074/jbc.271.25.15237.