A reduction in the activity of the NA⁺, K⁺ ‐pump in dimethylsulfoxide‐treated friend erythroleukemia cells is not due to partial inactivation of the NA⁺, K⁺ ‐ATPase

Abstract

Treatment of Friend-erythroleukemia cells with 1.5% dimethylsulfoxide (DMSO) caused a decrease in ouabain sensitive 86Rb+-uptake beginning six to seven hours after DMSO addition indicating a reduced function of the Na+, K+-pump. However, analysis of the ouabain sensitive 86Rb+-uptake after Na+-preloading of the cells as well as measurements on the Na+, K+-ATPase activity in isolated membrane fragments revealed that no inhibition of the Na+, K+-ATPase occurred during the first 12 hours. On the contrary the Na+, K+-ATPase activity was initially enhanced and then returned to control levels during the early phase of induction by DMSO. On the other hand, 22Na+-transport into DMSO-treated cells was reduced similar to the ouabain sensitive 86Rb+ uptake in cells without Na+ preloading. The piretanide sensitive 86Rb+-uptake, due to the Na+, K+, 2Cl - cotransport system was inhibited after seven hours exposure to DMSO. Some three hours after DMSO addition the incorporation of 35S-methionine into proteins began to decrease, which was accompanied with or followed by a reduction in the methionine uptake of DMSO treated cells. Membrane-potential-dependent tetraphenylphosphonium cation uptake was not altered relative to the controls in the first 12 hours following DMSO addition. These results suggest that the reduced activity of the Na+, K+-pump in Friend cells after DMSO exposure is not due to inhibition of the Na+, K+-ATPase, but most probably due to a smaller Na+-influx, which results from inhibition of Na+-cotransport processes (amino acid uptake, Na+, K+, 2Cl - cotransport system).

Interactions of dimethyl sulfoxide and granulocyte‐macrophage colony‐stimulating factors on the growth and maturation of HL‐60 cells

“…The decreased volume can be partially explained by the increased proportion of smaller GI cells relative to S and G2M cells in DMSO treated cultures. DMSO could also directly effect early volume changes by inhibiting Na + uptake with resultant fall in cell Na+ (Robinson, 1975;Schaefer et al, 1984;Faletto and Macara, 1985). The mechanism whereby GCT CM increases HL-60 cell volume in DMSO cultures may be due to the decreased GI cell proportion, although it appears that GCT CM by itself can increase HL-60 cell volume without necessarily altering cell cycle phase distributions as determined by DNA content.…”

Transport by the (Na+, K+) ATPase: Modulation by differentiation inducers and inhibition of protein synthesis in the MDCK kidney epithelial cell line

“…Thus, any of several different manipulations designed to raise Naf content (application of Na+ ionophores, stimulation of Naf/H+ antiport, increased Na' influx, partial inhibition of the sodium pump) can serve as a stimulus to cell differentiation (Bernstein et al, 1976;Kennedy and Lever, 1984;Rosoff and Cantley, 1983). Suggestions that the Naf/K+ pump inhibition after inducer treatment of Friend cells is a secondary effect resulting from inhibition of Na' influx via Naf cotransport processes (Schaefer et al, 1984) do not appear to apply to MDCK cells, since intracellular Na' levels were significantly elevated, not reduced, after inducer treatment (Kennedy and Lever, 1984).…”

Modulation of brain metabolism by very low concentrations of the commonly used drug delivery vehicle dimethyl sulfoxide (DMSO)

“…It should be noted that the response of cells to DMSO has a time‐dependent component. In Friend leukemia cells, DMSO stimulated the activity of the Na + /K + ATPase in the acute (up to 3 hr) phase, but this subsequently returned to control values (Schaefer et al, 1984) and was associated with a gradual reduction in Na + uptake and increased K + efflux. Mitochondria have been shown to regulate their gene expression acutely (i.e., on the same time scale as the present experiments) in response to energy demand, based on cellular Na + concentrations (Mehrabian et al, 2005).…”