Role of Ca2+ in stimulation of DNA synthesis by epidermal growth factor and tumor promoters in cultured rat hepatocytes

1993 ◽  
Vol 155 (1) ◽  
pp. 44-53 ◽  
Author(s):  
Tadija Petronijevic ◽  
Anthony M. Edwards
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.


2002 ◽  
Vol 25 (4) ◽  
pp. 437-440 ◽  
Author(s):  
Shingo Niimi ◽  
Mai Horikawa ◽  
Taiichiro Seki ◽  
Toyohiko Ariga ◽  
Tetsu Kobayashi ◽  
...  

1987 ◽  
Vol 247 (1) ◽  
pp. 233-235 ◽  
Author(s):  
S K Moule ◽  
J D McGivan

Epidermal growth factor causes a transient stimulation of alanine transport in hepatocytes. The stimulation is maximal after 30 min, and the rate returns to the control value after 90 min. These characteristics are very similar to the short-term stimulation of alanine transport by glucagon, which has been attributed to cell membrane hyperpolarization.


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