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 activity of electron transport chains in the mitochondria of HL-60 cells, the bioreduction rates of two membrane-localized lipophilic spin probes, 16-doxylstearic acid methyl ester (16-DSME) and 5-doxylstearic acid (5-DS), were studied. In addition, the effect of Pluronic on the bioreduction rate of the DNA-intercalating spin-labeled anthracyclin drug, Ruboxyl (Rb) was evaluated. For 16-DSME, the bioreduction kinetics was zero order with regard to the nitroxide concentration, indicating that the rate was controlled by the concentration 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 of 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, but did not follow any simple kinetic law after a short-term cell incubation with Pluronic. For Rb, the degree of nitroxide bioreduction dropped progressively 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.
Rapoport
N
N
Department of Bioengineering, University of Utah, Salt Lake City 84112, USA. natasha@rapoport@m.cc.utah.edu
Marin
A P
AP
Timoshin
A A
AA
D018943:Anthracyclines / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D003497:Cyclic N-Oxides / Q000378:metabolism; D003630:Daunorubicin / Q000031:analogs & derivatives* / Q000378:metabolism; D004578:Electron Spin Resonance Spectroscopy / Q000379:methods; D004579:Electron Transport / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D007364:Intercalating Agents / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D020442:Poloxamer / Q000494:pharmacology*; D011108:Polymers / Q000494:pharmacology; D013501:Surface-Active Agents / Q000494:pharmacology*; D013778:Tetrazolium Salts / Q000378:metabolism
C418525:16-doxylstearic acid methyl ester; D018943:Anthracyclines; D003497:Cyclic N-Oxides; D007364:Intercalating Agents; D011108:Polymers; D013501:Surface-Active Agents; D013778:Tetrazolium Salts; D020442:Poloxamer; C032363:16-nitroxystearic acid; C042480:ruboxyl; D003630:Daunorubicin