STIMULATION OF GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE MESSENGER-RNA LEVELS BY ENDOGENOUS NITRIC-OXIDE IN CYTOKINE-ACTIVATED ENDOTHELIUM

Previous studies have shown that endogenous nitric oxide (NO) potentiates glycolysis in the cytokine-activated murine microvascular endothelial cells (MME). In the present study we investigate the influence of NO on the expression of glyceraldehyde-3-phosphate dehydrogenase (GAPDH), an enzyme of the glycolytic pathway. Activation of MME with TNF-alpha and IFN-gamma resulted in a strong elevation of GAPDH mRNA levels. This effect was impaired in the presence of L-NMMA, the inhibitor of NO synthesis. We discuss the possibility that NO-mediated elevation of GAPDH mRNA levels may compensate for NO-mediated inhibition of GAPDH enzymatic activity, representing another adaptive mechanism which protects cells producing large amounts of NO against its cytotoxic effects. (C), 1995 Academic Press. Inc.