[Autocrine regulation of hexokinase activity by HB-EGF in mesangial cells].
OBJECTIVE
To investigate the influence of heparin-binding epidermal growth factor-like growth factor (HB-EFG) on the activity of hexokinases (HKs) in mesangial cells stimulated by phobal ester.


METHODS
SV40MES13 mesangial cell line was used as cell model and the total activity of HKs was measured by using standard G-6-PDH-coupled assay. Exogenous HB-EGF and phobal 12-myrisistate 13-acetate (PMA) conditioned medium in different concentrations were used to observe their influence on the activity of HKs. Tyrosine kinase inhibitor Genistein was used to observe its influence on the activation of HKs by HB-EGF and PMA.


RESULTS
Exogenous HB-EGF and PMA conditioned medium time- and dose-dependently induced the activity of HKs. The activity of HKs peaked 12 hours after the induction by HB-EGF and PMA (increased by 64.8% +/- 7.1% and 67.3% +/- 5.7%, P < 0.01) and peaked after the induction of HB-EGF at the concentration of 10nmol/L and PMA conditioned medium at the concentration by 100% (increased by 50.8% +/- 5.0 % and 57.0% +/- 7.7% respectively, P < 0.01). The tyrosine kinase inhibitor Genistein inhibited the induction of HKs activity by HB-EGF and conditioned medium.


CONCLUSIONS
HG-EGF induces the activity of HKs in mesangial cells. It may be involved in the abnormal carbohydrate metabolism in diabetic nephropathy.
Ma
J
J
Department of Nephrology, First Clinical College, China Medical University, Shenyang 110001, China.
Zhou
X
X
D000818:Animals; D002460:Cell Line; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D019833:Genistein / Q000494:pharmacology; D005920:Glomerular Mesangium / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D066257:Heparin-binding EGF-like Growth Factor; D006593:Hexokinase / Q000187:drug effects / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins; D051379:Mice; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D013997:Time Factors
D017077:Culture Media, Conditioned; C587884:Hbegf protein, mouse; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D004815:Epidermal Growth Factor; D019833:Genistein; D006593:Hexokinase; D066246:ErbB Receptors; D013755:Tetradecanoylphorbol Acetate