Stimulation of brain hexokinase gene expression by recombinant brain insulin-like growth factor in C6 glial cells.
Glycolysis is essential for cerebral energy generation. Hence, expression and regulation of gene-encoding brain hexokinase (HK I), the exclusive brain glucose phosphorylating enzyme, can be a critical step in this process. The present study demonstrates the ability of recombinant brain insulin-like growth factor (BIGF, a closely related member of insulin superfamily) to stimulate HK I gene expression in a concentration- and time-dependent manner in C6 glial cells. BIGF treatment (10 ng/ml) on quiescent C6 glial cells stimulates transcription and translation of HK I RNA to approximately 2.5-fold within 4 h after the addition of growth factor. In contrast, insulin or epidermal growth factor could not mimic this effect. Coincubation of cycloheximide with BIGF abolished this stimulatory effect, indicating a requirement for prior protein synthesis for this effect. These results suggest that IGF may have a role in regulating hexokinase gene expression in brain and possibly of brain glucose metabolism.
Sebastian
S
S
National Center for Cell Science, Pune University Campus, Pune-411 007, India. sebast11@pilot.msu.edu
Kenkare
U W
UW
D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D001921:Brain / Q000166:cytology / Q000201:enzymology*; D002460:Cell Line; D003513:Cycloheximide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004815:Epidermal Growth Factor / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006593:Hexokinase / Q000235:genetics* / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D009457:Neuroglia / Q000166:cytology* / Q000201:enzymology; D014176:Protein Biosynthesis; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology; D013997:Time Factors
D007328:Insulin; D011500:Protein Synthesis Inhibitors; D011994:Recombinant Proteins; D004815:Epidermal Growth Factor; D007334:Insulin-Like Growth Factor I; D003513:Cycloheximide; D006593:Hexokinase