Effect of a polymeric surfactant on electron transport in HL-60 cells

To assess the effect of a polymeric surfactant, Pluronic P-105 on the activ ity of electron transport chains in the mitochondria of HL-60 cells, the bi oreduction rates of two membrane-localized lipophilic spin probes, 16-doxyl stearic acid methyl ester (16-DSME) and 5-doxylstearic acid (5-DS), were st udied. In addition, the effect of Pluronic on the bioreduction rate of the DNA-intercalating spin-labeled anthracyclin drug, Ruboxyl (Rb) was evaluate d. For 16-DSME, the bioreduction kinetics was zero order with regard to the nitroxide concentration, indicating that the rate was controlled by the co ncentration of the reducing enzyme(s), which depends on the activity of the electron transport chains. The introduction of Pluronic at concentrations higher than 0.01% resulted in the decrease of the 16-DSME bioreduction rate . The data suggested that short-term cell incubation with Pluronic resulted in reduced activity of the electron transport chains in the mitochondria o f HL-60 cells. This was corroborated by the results of an MTT assay. For 5- DS, the bioreduction kinetics was first order in the absence of Pluronic, b ut did not follow any simple kinetic law after a short-term cell incubation with Pluronic. For Rb, the degree of nitroxide bioreduction dropped progre ssively with increasing Pluronic concentration. Thus, incubating cells with polymeric surfactants modulates the intracellular energy metabolism, which can affect the rates of energy-dependent intracellular processes. (C) 2000 Academic Press.