Modulation of glucose-related metabolic pathways controls glucose level in airway surface liquid and fight oxidative stress in cystic fibrosis cells.

Abstract

Direct and indirect evidences show that elevated glucose concentrations in airway surface liquid (ASL) promote lung infection by pathogens, playing a role in the progression of the Cystic Fibrosis (CF) disease. The joint action of transporter/s for glucose and of the cellular enzymes is essential in order to try to lower ASL glucose level. Inside the cell, the glycolysis and the pentose phosphate pathway (PPP) compete for the utilization of glucose-6-phosphate (G6P), the product in which glucose, after entry within the cell and phosphorylation, is trapped. The study aims to clarify whether, modulating the activity of enzymatic proteins and/or the level of metabolites/cofactors, involved in intracellular glucose utilization, a lowering of the extracellular glucose level in CF occurs. Biochemical approaches have enabled us to understand i) how G6P is shunted between glycolysis and PPP and ii) that mitochondria, more than enzymes/cofactors participating to the two cell glucose utilization pathways, are protagonists of the scene in counteracting the high ASL glucose level as well as oxidative stress in CF.