Genetic Deficiency of Glutathione S-Transferase P Increases Myocardial Sensitivity to Ischemia-Reperfusion Injury.

Rationale: Myocardial ischemia-reperfusion (I/R) results in the generation of oxygen-derived free radicals and the accumulation of lipid peroxidation-derived unsaturated aldehydes. However, the contribution of aldehydes to myocardial I/R injury has not been assessed.

Objective: We tested the hypothesis that removal of aldehydes by glutathione S-transferase P (GSTP) diminishes I/R injury.

Postischemic deactivation of cardiac aldose reductase: role of glutathione S-transferase P and glutaredoxin in regeneration of reduced thiols from sulfenic acids.

Aldose reductase (AR) is a multifunctional enzyme that catalyzes the reduction of glucose and lipid peroxidation-derived aldehydes. During myocardial ischemia, the activity of AR is increased due to the oxidation of its cysteine residues to sulfenic acids. It is not known, however, whether the activated, sulfenic form of the protein (AR-SOH) is converted back to its reduced, unactivated state (AR-SH).

Posttranslational glutathiolation of aldose reductase (AKR1B1): a possible mechanism of protein recovery from S-nitrosylation.

Nitric oxide (NO) is an important regulator of the catalytic activity of aldose reductase (AR). It reacts with the active site cysteines of AR and this reaction results in the formation of several kinetically distinct forms of the protein. The catalytic activity of AR is increased in the ischemic heart and this increase in activity is associated with NO-dependent modification of AR.