Plasma membrane ubiquinone controls ceramide production and prevents cell death induced by serum withdrawal.
Serum provides cultured cells with survival factors required to maintain growth. Its withdrawal induces the development of programmed cell death. HL-60 cells were sensitive to serum removal, and an increase of lipid peroxidation and apoptosis was observed. Long-term treatment with ethidium bromide induced the mitochondria-deficient rho(o)HL-60 cell line. These cells were surprisingly more resistant to serum removal, displaying fewer apoptotic cells and lower lipid peroxidation. HL-60 cells contained less ubiquinone at the plasma membrane than rho(o)HL-60 cells. Both cell types increased plasma membrane ubiquinone in response to serum removal, although this increase was much higher in rho(o) cells. Addition of ubiquinone to both cell cultures in the absence of serum improved cell survival with decreasing lipid peroxidation and apoptosis. Ceramide was accumulated after serum removal in HL-60 but not in rho(o)HL-60 cells, and exogenous ubiquinone reduced this accumulation. These results demonstrate a relationship between ubiquinone levels in the plasma membrane and the induction of serum withdrawal-induced apoptosis, and ceramide accumulation. Thus, ubiquinone, which is a central component of the plasma membrane electron transport system, can represent a first level of protection against oxidative damage caused by serum withdrawal.
Barroso
M P
MP
Departamento de Biología Celular, Facultad de Ciencias, Universidad de Córdoba, Spain.
Gómez-Díaz
C
C
Villalba
J M
JM
Burón
M I
MI
López-Lluch
G
G
Navas
P
P
D017209:Apoptosis; D002462:Cell Membrane / Q000502:physiology*; D002518:Ceramides / Q000096:biosynthesis*; D016895:Culture Media, Serum-Free / Q000494:pharmacology*; D003600:Cytosol / Q000378:metabolism; D004261:DNA Replication / Q000187:drug effects; D004272:DNA, Mitochondrial / Q000187:drug effects / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004996:Ethidium / Q000494:pharmacology; D018922:HL-60 Cells; D006801:Humans; D008054:Lipid Peroxides / Q000378:metabolism; D014451:Ubiquinone / Q000502:physiology*
D002518:Ceramides; D016895:Culture Media, Serum-Free; D004272:DNA, Mitochondrial; D004791:Enzyme Inhibitors; D008054:Lipid Peroxides; D014451:Ubiquinone; D004996:Ethidium