Sequential metabolic disturbances in IMS32 Schwann cells under high-glucose pyruvate-starved conditions. (IMAGE)
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Rapid and extensive Schwann cell death under high-glucose pyruvate-depleted conditions can be evoked by the following sequential metabolic alterations; 1) diminished TCA cycle intermediates and mitochondrial ATP production, 2) reduced GAPDH activity and inhibition of glycolytic flux through the activation of PARP, 3) escalation of the polyol and other collateral glycolysis pathways, 4) impaired hexokinase (HK) activity and glucose utilization in the glycolytic pathway, and 5) further escalation of the polyol pathway flux.
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