Enhanced antioxidant defenses and resistance to TNF-α 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 kappaB (NF-kappaB), 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-kappaB 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-kappaB activity. This acquired feature may compromise antineoplastic treatments based on glycolytic depletion. (C) 2002 Elsevier Science Inc.