Effect of ouabain on growth regulation by serum components in Balb/c-3T3 cells: inhibition of entry into S phase by decreased protein synthesis.
The effect of inhibition of the cell membrane Na+-K+ pump on the Balb/c-3T3 cell growth cycle was studied. Inhibition of the Na+-K+ pump resulted in a dose-dependent reduction of intracellular K+ concentration ((K+)i). However, inhibition of protein synthesis in Go/G1 and of subsequent entry into S phase occurred only after (K+)i fell below a critical threshold (50-60 mmoles/liter). Thus, when the (K+)i falls below a critical threshold, protein synthesis is inhibited, preventing cells from entering the S phase. The platelet-derived growth factor (PDGF) induces cells to become "competent" to traverse the cell cycle; the platelet-poor plasma component of serum allows competent cells to progress through G0/G1 and enter S phase. Inhibition of the Na+-K+ pump did not prevent the induction of competence by PDGF, but it did reversibly inhibit plasma-mediated events in early G0/G1. Similarly, cycloheximide inhibited plasma-mediated events but did not prevent PDGF-induced competence. Thus, protein synthesis may not be required for induction of competence; alternatively, the induction of the competent state may occur in these cells after removal of PDGF and protein synthesis inhibitor. Protein synthesis is required for subsequent plasma-mediated events in G0/G1.
D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001792:Blood Platelets / Q000502:physiology; D002453:Cell Cycle / Q000187:drug effects*; D002478:Cells, Cultured; D004261:DNA Replication / Q000187:drug effects; D006131:Growth Inhibitors; D006133:Growth Substances / Q000097:blood; D051379:Mice; D010042:Ouabain / Q000494:pharmacology*; D011188:Potassium / Q000502:physiology*; D014176:Protein Biosynthesis; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors
D000596:Amino Acids; D006131:Growth Inhibitors; D006133:Growth Substances; D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium