Enhanced antioxidant defenses and resistance to TNF-alpha in a glycolysis-depleted lung epithelial cell line.
Glycolysis-depleted cells, obtained by stable transfection of fructose 2,6-bisphosphatase in mink lung epithelial cells (Mv1Lu), were less sensitive to serum withdrawal- and TNF-alpha-induced apoptosis than cells transfected with the empty vector pcDNA3 (control cells). We compared the differences in the redox status of the two transfectants and the changes produced by TNF-alpha treatment. The activities of the antioxidant enzymes catalase and glutathione peroxidase, as well as the content of reduced glutathione (GSH) and the activity of the nuclear transcription factor kappa B (NF-kappa B), were higher in pFBPase-2 clones than in control cells in all the conditions tested. TNF-alpha challenge sharpened the differences in glutathione peroxidase activity, GSH/GSSG ratios, and NF-kappa B activation between transfectants. These data indicate that glycolysis restriction at the PFK step protects cells against apoptotic stimuli by increasing the GSH content and NF-kappa B activity. This acquired feature may compromise antineoplastic treatments based on glycolytic depletion.
Boada
Jordi
J
Departament de Ciències Fisiològiques II, Divisió de Ciències de la Salut, Universitat de Barcelona, Barcelona, Spain.
Cuesta
Eduardo
E
Roig
Teresa
T
Gámez
Antonio
A
Carbonell
Teresa
T
Ventura
Francesc
F
Bermúdez
Jordi
J
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D002469:Cell Separation; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000378:metabolism*; D005434:Flow Cytometry; D005721:Glutamate-Cysteine Ligase / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D006019:Glycolysis; D008156:Luciferases / Q000378:metabolism; D008168:Lung / Q000378:metabolism*; D008907:Mink; D016328:NF-kappa B / Q000378:metabolism; D010084:Oxidation-Reduction; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D001616:beta-Galactosidase / Q000378:metabolism
D000975:Antioxidants; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D005979:Glutathione Peroxidase; D008156:Luciferases; D001616:beta-Galactosidase; D005721:Glutamate-Cysteine Ligase; D005978:Glutathione