Hypoxia Cell Metabolism and cADPR Accumulation

Authors: A Mark Evans

Publish Date: 2004

Volume: , Issue: , Pages: 313-338

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Abstract

In summary it is clear that hypoxia promotes pulmonary artery constriction via the activation of a “metabolic sensors” and a “primary effectors” The “primary effector” may then modulate a variety of other cell functions associated with HPV including cADPR accumulation Hypoxia likely triggers these events by inhibiting oxidative phosphorylation by mitochondria leading to an increase in cytoplasmic AMP levels as the adenylate kinase reaction seeks to maintain ATP levels I propose that a build up of AMP leads to the activation of the primary “metabolic sensors/primary effectors” in O2sensing cells namely AMPK kinase and AMPK respectively and that AMPK in addition to promoting glucose uptake and anaerobic glycolysis may activate ADPribosyl cyclase and cADPR accumulation by hypoxia Subsequently increased βNADH formation by anaerobic glycolysis may augment cADPR accumulation As the severity of hypoxia increases however βNADH levels may increase still further leading to a consequent fall in cADPR levels due to reduced substrate availability βNAD+ and ultimately to the failure of maintained HPV Fig 5 While I cannot rule out the possibility that a paradoxical increase in mitochondrial ROS by hypoxia may also promote cADPR accumulation this seems unlikely

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