Norepinephrine and epidermal growth factor: Dynamics of their interaction in the stimulation of hepatocyte DNA synthesis

1985 ◽  
Vol 125 (1) ◽  
pp. 45-50 ◽  
Author(s):  
Jennifer L. Cruise ◽  
George Michalopoulos
1984 ◽  
Vol 98 (3) ◽  
pp. 1082-1089 ◽  
Author(s):  
C P Burns ◽  
E Rozengurt

Initiation of DNA synthesis in confluent quiescent 3T3 cell cultures stimulated by epidermal growth factor (EGF), vasopressin, and insulin was abolished by removing extracellular Na+. The inhibition was reversible, time- and Na+-concentration-dependent, and not due to an effect on binding or internalization of 125I-EGF. Stimulation by combinations of other growth factors with different mechanisms of action was also affected by decreasing extracellular Na+, but with different half-maximal Na+ concentrations. When choline was used as an osmotic substitute for Na+, the decrease in DNA synthesis was correlated with the decrease in intracellular K+. In contrast, when sucrose was used there was stimulation of the Na+-K+ pump and maintenance of intracellular K+ that resulted in a somewhat higher rate of DNA synthesis at lowered extracellular Na+ compared to choline. Mitogenesis induced by epidermal growth factor, vasopressin, and insulin led to cytoplasmic alkalinization as determined by an increase in uptake of the weak acid 5,5-dimethyloxazolidine-2,4-dione. Experimental decrease in extracellular Na+ blocked this cellular alkalinization. Therefore, under some conditions the supply of extracellular Na+ may limit cellular proliferation because of a reduction in the provision of Na+ to the Na+/H+ antiport and resultant failure of alkalinization. We conclude that Na+ flux and its effect on intracellular K and pH has a major role in the complex system that regulates proliferation.


Development ◽  
1980 ◽  
Vol 60 (1) ◽  
pp. 235-243
Author(s):  
Geoffrey V. Goldin ◽  
Lynne A. Opperman

Epidermal growth factor (EGF) has been found to stimulale DNA synthesis in both the trachea and bronchial tree of 5-day-old chick embryo lung rudiments in organ culture. After 20 h culture in the presence of 10 ng/ml EGF, the incorporation of tritiated thymidine into DNA is stimulated two- to three-fold following a 2 h labelling period, as revealed by scintillation counting. Autoradiographic data indicate that this stimulation is most marked in the epithelial tissue component of both the trachea and bronchial tree. Supernumerary ‘lung’ buds have been induced in the normally unbranched tracheal epithelium by agarose pellets containing EGF, such buds having been previously induced only by grafting a variety of mesenchymal tissues alongside the tracheal epithelium. Since EGF has been shown to be a potent stimulator of tracheal DNA synthetic activity it is suggested that the induction of supernumerary buds by the EGF-agarose pellets is achieved through a localized stimulation of cell proliferation in the tracheal epithelium. These data would further suggest that the induction of supernumerary tracheal buds by various mesenchymal tissues is similarly due to a localized increase in mitotic activity resulting from the action of some mitotic stimulator substance(s) emanating from the inducing mesenchymal tissue. This conclusion may be extended to include normal bud formation which occurs during branching morphogenesis in everal developing organ systems.


Development ◽  
1980 ◽  
Vol 58 (1) ◽  
pp. 93-106
Author(s):  
Mary S. Tyler ◽  
Robert M. Pratt

Previous studies have shown that epidermal growth factor (EGF), a peptide of m.w. 6045, can specifically inhibit in organ culture the cessation of DNA synthesis and programmed cell death that normally occur in the presumptive fusion zone (PFZ) of the secondary palatal epithelium. The aim of this study was to determine if EGF acts directly on the epithelium to exert its effect and if there is a requirement for the underlying mesenchyme. Palatal processes from 13- and 14-day Swiss Webster embryonic mice were enzymatically separated into epithelium and mesenchyme which were then cultured alone or in transfilter recombination for up to 72 h. Tissues were examined by transmission- and scanning-electron microscopy and DNA synthesis was monitored autoradiographically using [3H]thymidine incorporation. In isolated epithelium cultured in control medium, cell death occurred in the PFZ and DNA synthesis did not occur in the oral and nasal epithelial regions. EGF (20–50 ng/ml) did not prevent cell death in the PFZ and failed to stimulate DNA synthesis in the isolated epithelium; EGF, however, did have an effect on epithelial cell morphology. In the presence of mesenchyme and EGF, there was extensive proliferation in the entire epithelium and cell death within the PFZ was not evident. The results indicate that the stimulation of DNA synthesis in the palatal epithelium by EGF requires the presence of the underlying mesenchyme and that EFG alone is not sufficient to inhibit programmed cell death within the PFZ of the isolated palatal epithelium.


1983 ◽  
Vol 35 (1) ◽  
pp. 624-628 ◽  
Author(s):  
K. W. Ng ◽  
N. C. Partridge ◽  
M. Niall ◽  
T. J. Martin

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