Article (Scientific journals)
Glyceraldehyde-3-phosphate dehydrogenase regulates activation of c-Jun N-terminal kinase under oxidative stress
ITAKURA, Masanori; Kubo, Takeya; Kaneshige, Akihiro et al.
2023In Biochemical and Biophysical Research Communications, 657, p. 1-7
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Abstract :
[en] Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) acts as a sensor under oxidative stress, leading to induction of various biological responses. Given that mitogen-activated protein kinase (MAPK) signaling pathways mediate cellular responses to a wide variety of stimuli, including oxidative stress, here, we aimed to elucidate whether a cross-talk cascade between GAPDH and MAPKs occurs under oxidative stress. Of the three typical MAPKs investigated—extracellular signal-regulated kinase, p38, and c-Jun N-terminal kinase (JNK)—we found that hydrogen peroxide (H2O2)-induced JNK activation is significantly reduced in HEK293 cells treated with small-interfering (si)RNA targeting GAPDH. Co-immunoprecipitation with a GAPDH antibody further revealed protein–protein interactions between GAPDH and JNK in H2O2-stmulated cells. Notably, both JNK activation and these interactions depend on oxidation of the active-site cysteine (Cys152) in GAPDH, as demonstrated by rescue experiments with either exogenous wild-type GAPDH or the cysteine-substituted mutant (C152A) in endogenous GAPDH-knockdown HEK293 cells. Moreover, H2O2-induced translocation of Bcl-2-associated X protein (Bax) into mitochondria, which occurs downstream of JNK activation, is attenuated by endogenous GAPDH knockdown in HEK293 cells. These results suggest a novel role for GAPDH in the JNK signaling pathway under oxidative stress.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
ITAKURA, Masanori  ;  University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Neuroinflammation Group
Kubo, Takeya
Kaneshige, Akihiro
Nakajima, Hidemitsu
External co-authors :
yes
Language :
English
Title :
Glyceraldehyde-3-phosphate dehydrogenase regulates activation of c-Jun N-terminal kinase under oxidative stress
Publication date :
2023
Journal title :
Biochemical and Biophysical Research Communications
ISSN :
0006-291X
eISSN :
1090-2104
Publisher :
Elsevier, Atlanta, Us ca
Volume :
657
Pages :
1-7
Peer reviewed :
Editorial Reviewed verified by ORBi
Available on ORBilu :
since 29 November 2023

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