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Subapoptogenic Oxidative Stress Strongly Increases the Activity of the Glycolytic Key Enzyme Glyceraldehyde 3‐Phosphate Dehydrogenase
Author(s) -
Cerella Claudia,
D’Alessio Maria,
Cristofa Silvia,
De Nicola Milena,
Radogna Flavia,
Dicato Mario,
Diederich Marc,
Ghibelli Lina
Publication year - 2009
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2009.04723.x
Subject(s) - glyceraldehyde 3 phosphate dehydrogenase , glycolysis , oxidative stress , dehydrogenase , flux (metallurgy) , chemistry , pentose phosphate pathway , programmed cell death , biochemistry , microbiology and biotechnology , glyceraldehyde , glutathione , u937 cell , enzyme , apoptosis , biology , organic chemistry
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.