Table 2.
Proteins Reported to Undergo S-Glutathionylation and Implicated in Diabetes
| Protein | Function | Oxidizing stimulus | Milieu | Reference for glutathionylation | Implication in diabetes | Reference |
|---|---|---|---|---|---|---|
| Alcohol dehydrogenase | Catalyzes alcohol metabolism | GSH + diamide, or GSNO | In vitro | 155 | Increased activity in male rats | 54a |
| *Cu, Zn SOD | Catalyzes superoxide dismutation | GSH + diamide or GSNO; Decomposed GSNO | In vitro; In vitro | 155, 292a | Protect against alloxan-induced b-cell death | 107a |
| Malate dehydrogenase | Catalyzes malate-aspartate shuttle | Rose Bengal + 1 min white light | Heart homogenates | 79a | Decreased activity in leukocytes of dogs | 11a |
| Creatine kinase | Catalyzes creatine-P formation | GSH + diamide, or GSNO | In vitro | 155 | Decreased activity in rat heart | 239a |
| Glycogen phosphorylase b | Catalyzes glycogenolysis | GSH + diamide, or GSNO | In vitro | 155 | Eminent therapeutic target | 305a, 219a |
| Calbindin | Binds/regulates calcium | Decomposed GSNO | In vitro | 292a | Protects pancreatic b cells from death | 243a |
| Cathepsin K | Catabolism of bone & cartilage | GSNO | In vitro | 233b | Increased activity in rat bone | 117a |
| Fatty acid binding protein | Intracellular transporters in lipid metabolism | T cell blasts | Diamide + CHX | 89a | Increased levels in patients | 111a |
| HSP60 | Chaperones in protein folding | T cell blasts | Diamide + CHX | 89a | Downregulated in muscle | 38a |
| Pro-caspase 3 | Signals apoptotic cell death | GSH + diamide, or GSNO; TNFa + CHX | In vitro, Endothelial cells | 155, 227 | Activation & proliferation of b cell-specific T cells; activated in diabetic retinae | 170a, 202a |
| GAPDH | Housekeeping and cell signaling protein | Decomposed GSNO | In vitro | 292a | Inhibition leads to PKC activation, hexosamine flux, and AGEs in endothelial cells in high glucose | 77 |
| Hemoglobin | Transports oxygen | Diabetes | Human Subjects | 262 | Elevated in diabetic patients | 262 |
Altered protein function via S-glutathionylation may have impact on many different pathological areas in diabetes, but changes in S-glutathionylation status corresponding to functional differences and reversibility by glutaredoxin need to be documented.
*
Glutathionylation studies used CuZnSOD, but the type of SOD was not specified in the diabetes study. CHX, cycloheximide; GSH, glutathione; GSNO, nitrosylated glutathione, TNFα, tumor necrosis factor-alpha.