H2O2-induced block of glycolysis as an active ADP-ribosylation reaction protecting cells from apoptosis

[摘要] H2O2 treatment on U937 cells leads to the block of glycolytic flux and the inactivation of glyceraldehyde-3-phosphate-dehydrogenase by a posttranslational modification (possibly ADP-ribosylation), Glycolysis spontaneously reactivates after 2 h of recovery from oxidative stress; thereafter cells begin to undergo apoptosis, The specific ADP-ribosylation inhibitor 3-aminobenzamide inhibits the stress-induced inactivation of glyceraldehyde-3-phosphate-dehydrogenase and the block of glycolysis; concomitantly, it anticipates and increases apoptosis, Exogenous block of glycolysis (i.e., by culture in glucose-free medium or with glucose analogs or after NAD depletion), turns the transient block into a stable one: this results in protection from apoptosis, even when downstream cell metabolism is kept active by the addition of pyruvate, All this evidence indicates that the stress-induced block of glycolysis is not the result of a passive oxidative damage, but rather an active cell reaction programmed via ADP-ribosylation for cell self-defense.-Colussi, C., Albertini, M. C., Coppola, S., Rovidati, S., Galli, F., Ghibelli, L. H2O2-induced block of glycolysis as an active ADP-ribosylation reaction protecting cells from apoptosis.

[发布日期] 2000-11-01

[关键词] NICOTINAMIDE ADENINE-DINUCLEOTIDE;ISLET-ACTIVATING PROTEIN;GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE;HYDROGEN-PEROXIDE;NITRIC-OXIDE;COVALENT MODIFICATION;MAMMALIAN-CELLS;S-NITROSYLATION;INDUCED INJURY;GSH EXTRUSION