Enhanced glycolysis causes extracellular acidification and activates acid-sensing ion channel 1a in hypoxic pulmonary hypertension
Megan N. Tuineau, Lindsay M. Herbert, Selina M. Garcia, Thomas C. Resta, Nikki L. Jernigan
2024American Journal of Physiology-Lung Cellular and Molecular Physiology18 citationsDOIOpen Access PDF
Abstract
In pulmonary hypertension, a metabolic shift to aerobic glycolysis drives a hyperproliferative, apoptosis-resistant phenotype in pulmonary arterial smooth muscle cells. We demonstrate that this enhanced glycolysis induces extracellular acidosis and activates the proton-gated ion channel, acid-sensing ion channel 1a (ASIC1a). Although multiple H + transport/secretion mechanisms are upregulated in PHTN and likely contribute to extracellular acidosis, inhibiting glycolysis with 2-deoxy-d-glucose or syrosingopine effectively prevents extracellular acidification and ASIC1a activation, revealing a promising therapeutic avenue.
Topics & Concepts
Pulmonary hypertensionExtracellularGlycolysisHypoxia (environmental)ChemistryIon channelCell biologyBiophysicsCardiologyMedicineBiochemistryBiologyMetabolismOxygenReceptorOrganic chemistryPulmonary Hypertension Research and TreatmentsMitochondrial Function and PathologyIon Transport and Channel Regulation