Subapoptogenic oxidative stress strongly increases the activity of the glycolytic key enzyme glyceraldehyde 3-phosphate dehydrogenase.
We have previously shown that oxidative stress induced by an apoptogenic dose of H(2)O(2) leads to a temporary block of glycolytic flux via inactivation of the glycolytic key enzyme glyceraldehyde 3-phosphate dehydrogenase (GAPDH) in U937 cells. This corresponds to the activation of a cell defense pathway that is triggered to repair stress-induced damage and to rescue cells from death. Here, we show that subapoptogenic doses of H(2)O(2) affect GAPDH activity in an opposite way, leading to strong hyperactivation. This phenomenon is related to milder oxidative stress because induction of a moderate oxidative stress with an alternative approach (i.e., by decreasing glutathione content in the cells with buthionine sulphoximine) gives similar results. U937 cells hyperactivate GAPDH with the same timing observed for GAPDH alterations from apoptogenic doses of H(2)O(2). Additionally, the prevention of the glycolytic flux sensitizes stressed cells to apoptosis. This suggests that GAPDH hyperactivity might also be an active cell response to stress, thus depicting multiple roles for glycolytic flux in different prosurvival pathways where activation depends on the strength of the oxidative stress.
Cerella
Claudia
C
Laboratoire de Biologie Moléculaire et Cellulaire du Cancer, Hôpital Kirchberg, Luxembourg. claudia.cerella@lbmcc.lu
D'Alessio
Maria
M
Cristofanon
Silvia
S
De Nicola
Milena
M
Radogna
Flavia
F
Dicato
Mario
M
Diederich
Marc
M
Ghibelli
Lina
L
D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000378:metabolism*; D006019:Glycolysis / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress / Q000502:physiology*; D020298:U937 Cells
D000964:Antimetabolites, Antineoplastic; D016877:Oxidants; D019328:Buthionine Sulfoximine; D006861:Hydrogen Peroxide; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases