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.
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.
Authors: A Sola; J De Oca; R González; N Prats; J Roselló-Catafau; E Gelpí; E Jaurrieta; G Hotter Journal: Ann Surg Date: 2001-07 Impact factor: 12.969