Modification of glyceraldehyde-3-phosphate dehydrogenase in response to nitric oxide in intestinal preconditioning

Background Previous studies have demonstrated that intestinal preconditioning is triggered by an initial increase in nitric oxide synthesis. This confers resistance to the organ in face of a subsequently sustained period of ischemia-reperfusion. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a key enzyme in the glycolytic cascade that could be modulated by nitric oxide. The purpose of the present study is to evaluate a possible inhibitory effect on intestinal GAPDH by the nitric oxide generated during preconditioning. This could lead to a reduction of lactate accumulation during subsequent ischemia. Methods. GAPDH activity was measured after intestinal preconditioning, and the effect of nitric oxide synthase inhibition was evaluated. Results. Preconditioning induced a significant, but transient, decrease in GAPDH activity. This effect appears to be correlated with a reduced amount of lactate accumulation during ischemia. Inhibition of nitric oxide synthesis reversed these changes. In addition, increased synthesis of nitric oxide was detected after preconditioning. Conclusions. In summary, this study indicates that nitric oxide generated during ischemic preconditioning could act as a glycolytic modulator during subsequent ischemia, through its effect on GAPDH activity.