S-glutathionylation of glyceraldehyde-3-phosphate dehydrogenase: role of thiol oxidation and catalysis by glutaredoxin.
The findings in this article illustrate the complexity residing in the regulation of reversible S-glutathionylation of proteins, such as GAPDH. This is clearly reflected in the design of suitable experimental approaches designed to cope with the interaction of several redox-dependent factors. Clear interactions are demonstrated between oxidative modification of GAPDH and its subsequent S-glutathionylation. Similarly, a redox interaction between GSSG and GAPDH with Grx as the catalyst is shown, suggesting that the Grx molecule may participate in catalytic S-glutathionylation in intact cells. Furthermore, Grx itself can readily undergo S-glutathionylation, indicating the potential for regulation of this catalyst of the reversible S-glutathionylation of other proteins. The methodologies detailed in this work may provide a good reference point for other attempts to elucidate the mechanism of reversible S-glutathionylation of purified proteins in a manner that more closely resembles the situation arising in intact cells during the generation of oxidative stress.
Cotgreave
Ian A
IA
Biochemical Toxicology Unit, Institute of Environmental Medicine, Karolinska Institute, S-17177 Stockholm, Sweden.
Gerdes
Robert
R
Schuppe-Koistinen
Ina
I
Lind
Christina
C
D001345:Autoradiography; D002384:Catalysis; D004926:Escherichia coli / Q000201:enzymology; D054477:Glutaredoxins; D005978:Glutathione / Q000737:chemistry / Q000378:metabolism*; D019803:Glutathione Disulfide / Q000737:chemistry / Q000378:metabolism; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D010084:Oxidation-Reduction; D010088:Oxidoreductases; D011506:Proteins / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000737:chemistry / Q000378:metabolism
C516005:GLRX protein, human; D054477:Glutaredoxins; D011506:Proteins; D011994:Recombinant Proteins; D013438:Sulfhydryl Compounds; D010088:Oxidoreductases; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D005978:Glutathione; D019803:Glutathione Disulfide