Coenzyme Q and the regulation of intracellular steady-state levels of superoxide in HL-60 cells.
The present work was set to study how CoQ concentrations affected steady-state levels of superoxide in a cellular model of partial CoQ(10) deficiency in cultured human myeloid leukemia HL-60 cells. Culturing HL-60 cells in the presence of p-aminobenzoate, a competitive inhibitor of polyprenyl-4-hydroxybenzoate transferase (Coq2p), produced a significant decrease of CoQ(10) levels without affecting cell viability. Concomitant decreases in CoQ-dependent electron transport activity and mitochondrial membrane potential were observed under these conditions. Intracellular superoxide was significantly elevated in cells treated with p-aminobenzoate, both under serum-containing and serum-free conditions, and this effect was reversed by exogenous CoQ(10). A slight increase of superoxide was also observed in CoQ(10)-supplemented cells in the absence of serum. Our results support a requirement for CoQ(10) to control superoxide levels in HL-60 cells. The importance of extramitochondrial sources of superoxide in cells with impaired CoQ(10) biosynthesis is discussed.
González-Aragón
David
D
Departamento de Biología Celular, Fisiología e Inmunología, Universidad de Córdoba, Spain.
Burón
María I
MI
López-Lluch
Guillermo
G
Hermán
María D
MD
Gómez-Díaz
Consuelo
C
Navas
Plácido
P
Villalba
José M
JM
D010129:4-Aminobenzoic Acid / Q000494:pharmacology; D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors*; D003067:Coenzymes; D018922:HL-60 Cells; D006801:Humans; D010617:Phenanthridines / Q000378:metabolism; D013384:Succinate Cytochrome c Oxidoreductase / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism*; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000172:deficiency / Q000502:physiology
D003067:Coenzymes; D010617:Phenanthridines; D013481:Superoxides; D014451:Ubiquinone; C058428:hydroethidine; D013384:Succinate Cytochrome c Oxidoreductase; D019883:Alkyl and Aryl Transferases; C021386:4-hydroxybenzoate polyprenyltransferase; C024989:coenzyme Q10; D010129:4-Aminobenzoic Acid