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Extracellular Na+ and initiation of DNA synthesis: role of intracellular pH and K+

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 interna...

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Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 1984
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2113146/
https://www.ncbi.nlm.nih.gov/pubmed/6699083
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collection PubMed
description 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.
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spelling pubmed-21131462008-05-01 Extracellular Na+ and initiation of DNA synthesis: role of intracellular pH and K+ J Cell Biol Articles 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. The Rockefeller University Press 1984-03-01 /pmc/articles/PMC2113146/ /pubmed/6699083 Text en This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Articles
Extracellular Na+ and initiation of DNA synthesis: role of intracellular pH and K+
title Extracellular Na+ and initiation of DNA synthesis: role of intracellular pH and K+
title_full Extracellular Na+ and initiation of DNA synthesis: role of intracellular pH and K+
title_fullStr Extracellular Na+ and initiation of DNA synthesis: role of intracellular pH and K+
title_full_unstemmed Extracellular Na+ and initiation of DNA synthesis: role of intracellular pH and K+
title_short Extracellular Na+ and initiation of DNA synthesis: role of intracellular pH and K+
title_sort extracellular na+ and initiation of dna synthesis: role of intracellular ph and k+
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2113146/
https://www.ncbi.nlm.nih.gov/pubmed/6699083