PMID- 21827172
OWN - NLM
STAT- MEDLINE
DCOM- 20120402
LR  - 20131121
IS  - 1520-5010 (Electronic)
IS  - 0893-228X (Linking)
VI  - 24
IP  - 11
DP  - 2011 Nov 21
TI  - GSH-mediated S-transarylation of a quinone glyceraldehyde-3-phosphate 
      dehydrogenase conjugate.
PG  - 1836-44
LID - 10.1021/tx200025y [doi]
AB  - Many cellular proteins with reactive thiols form covalent bonds with 
      electrophiles, thereby modifying their structures and activities. Here, we 
      describe the recovery of a glycolytic protein, glyceraldehyde-3-phosphate 
      dehydrogenase (GAPDH), from such an electrophilic attack by 1,2-napthoquinone 
      (1,2-NQ). GAPDH readily formed a covalent bond with 1,2-NQ through Cys152 at a 
      low concentration (0.2 muM) in a cell-free system, but when human epithelial A549 
      cells were exposed to this quinone at 20 muM, only minimal binding was observed 
      although extensive binding to numerous other cellular proteins occurred. 
      Depletion of cellular glutathione (GSH) with buthionine sulfoximine (BSO) 
      resulted in some covalent modification of cellular GAPDH by 1,2-NQ and a 
      significant reduction of GAPDH activity in the cells. Incubation of native, but 
      not boiled, human GAPDH that had been modified by 1,2-NQ with GSH resulted in a 
      concentration-dependent removal of 1,2-NQ from the GAPDH conjugate, accompanied 
      by partial recovery of lost catalytic activity and formation of a 1,2-NQ-GSH 
      adduct (1,2-NQ-SG). While GAPDH is recognized as a multifunctional protein, our 
      results show that GAPDH also has a unique ability to recover from electrophilic 
      modification by 1,2-NQ through a GSH-dependent S-transarylation reaction.
FAU - Miura, Takashi
AU  - Miura T
AD  - Doctoral Program in Biomedical Sciences, Graduate School of Comprehensive Human 
      Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.
FAU - Kakehashi, Hidenao
AU  - Kakehashi H
FAU - Shinkai, Yasuhiro
AU  - Shinkai Y
FAU - Egara, Yuko
AU  - Egara Y
FAU - Hirose, Reiko
AU  - Hirose R
FAU - Cho, Arthur K
AU  - Cho AK
FAU - Kumagai, Yoshito
AU  - Kumagai Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110901
PL  - United States
TA  - Chem Res Toxicol
JT  - Chemical research in toxicology
JID - 8807448
RN  - 0 (Naphthoquinones)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Sulfhydryl Compounds)
RN  - 5072-26-4 (Buthionine Sulfoximine)
RN  - 804K62F61Q (1,2-naphthoquinone)
RN  - EC 1.2.1.- (Glyceraldehyde-3-Phosphate Dehydrogenases)
RN  - GAN16C9B8O (Glutathione)
SB  - IM
MH  - Buthionine Sulfoximine/adverse effects/pharmacology
MH  - Cell Line
MH  - Cell-Free System
MH  - Cloning, Molecular
MH  - Epithelial Cells/drug effects/*enzymology
MH  - Escherichia coli
MH  - Glutathione/*metabolism
MH  - Glyceraldehyde-3-Phosphate Dehydrogenases/chemistry/genetics/*metabolism
MH  - Glycolysis/drug effects/genetics
MH  - Humans
MH  - Mutation
MH  - Naphthoquinones/chemistry/*metabolism
MH  - Oxidation-Reduction/drug effects
MH  - Plasmids
MH  - Protein Denaturation
MH  - Protein Processing, Post-Translational
MH  - Recombinant Proteins/chemistry/genetics/*metabolism
MH  - Sulfhydryl Compounds/chemistry/*metabolism
MH  - Transformation, Bacterial
EDAT- 2011/08/11 06:00
MHDA- 2012/04/03 06:00
CRDT- 2011/08/11 06:00
PHST- 2011/08/11 06:00 [entrez]
PHST- 2011/08/11 06:00 [pubmed]
PHST- 2012/04/03 06:00 [medline]
AID - 10.1021/tx200025y [doi]
PST - ppublish
SO  - Chem Res Toxicol. 2011 Nov 21;24(11):1836-44. doi: 10.1021/tx200025y. Epub 2011 
      Sep 1.