H2O2-induced block of glycolysis as an active ADP-ribosylation reaction protecting cells from apoptosis.
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
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C
Dipartimento di Biologia, Università di Roma Tor Vergata; 00133, Rome, Italy.
Albertini
M C
MC
Coppola
S
S
Rovidati
S
S
Galli
F
F
Ghibelli
L
L
D017209:Apoptosis / Q000187:drug effects*; D001549:Benzamides / Q000494:pharmacology; D003847:Deoxyglucose / Q000494:pharmacology; D004734:Energy Metabolism / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D005047:Etoposide / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000378:metabolism; D006019:Glycolysis / Q000187:drug effects*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D007773:Lactates / Q000378:metabolism; D018384:Oxidative Stress; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D011691:Puromycin / Q000494:pharmacology; D013997:Time Factors; D020298:U937 Cells
D001549:Benzamides; D007773:Lactates; D011691:Puromycin; D005047:Etoposide; C025160:3-aminobenzamide; D003847:Deoxyglucose; D006861:Hydrogen Peroxide; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D011065:Poly(ADP-ribose) Polymerases; D005947:Glucose