Relationship of the decreases in protein synthesis and intracellular Na+ during friend murine erythroleukemic cell differentiation.
The earliest known ionic event during Friend murine erythroleukemic (MEL) cell differentiation along the erythroid pathway is a 45% drop in intracellular sodium concentration ([Na+]i) due to a decrease in Na+ influx (Lannigan, D. A., and Knauf, P. A. (1985) J. Biol. Chem. 260, 7322-7324). We have analyzed the mechanism of the decreased Na+ influx. The Na+ influx in uninduced cells was insensitive to dimethylamiloride, bumetanide, and diisothiocyanostilbene disulfonate. The intracellular pH (pHi) did not change up to 15 h after dimethyl sulfoxide induction, at which time Na+ influx has decreased by approximately 40%; thus, the decrease in Na+ influx is not coupled to a change in pHi. A substantial amount of the decrease in Na+ influx seems to result from a drop in amino acid-dependent Na+ transport. This reduction in amino acid-dependent Na+ influx reflects a decrease in net Na+ influx rather than solely in Na+/Na+ exchange and can account for an appreciable portion of the reduction in [Na+]i seen during differentiation. The drop in amino acid-dependent Na+ influx could not be explained by membrane depolarization but was correlated with a decrease in protein synthesis. Inhibition of protein synthesis in uninduced cells by cycloheximide also caused a decrease in Na+ influx. We conclude that during differentiation the reduction in protein synthesis decreases amino acid-dependent Na+ influx which in turn causes a drop in [Na+]i leading to a reduction in the Na+/K+ pump rate.
Lannigan
D A
DA
Knauf
P A
PA
Macara
I G
IG
D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D003513:Cycloheximide / Q000494:pharmacology; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D004915:Leukemia, Erythroblastic, Acute / Q000378:metabolism* / Q000473:pathology; D007942:Leukemia, Experimental / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D009861:Onium Compounds / Q000378:metabolism; D009943:Organophosphorus Compounds / Q000378:metabolism; D012964:Sodium / Q000378:metabolism*
D000596:Amino Acids; D009363:Neoplasm Proteins; D009861:Onium Compounds; D009943:Organophosphorus Compounds; D003513:Cycloheximide; D012964:Sodium; C013289:tetraphenylphosphonium; D004121:Dimethyl Sulfoxide