RNA SEQ Analysis Indicates that the AE3 Cl−/HCO3 − Exchanger Contributes to Active Transport-Mediated CO2 Disposal in Heart

Abstract Loss of the AE3 Cl−/HCO3 − exchanger (Slc4a3) in mice causes an impaired cardiac force-frequency response and heart failure under some conditions but the mechanisms are not known. To better understand the functions of AE3, we performed RNA Seq analysis of AE3-null and wild-type mouse hearts...

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Autores principales:	Kanimozhi Vairamani, Hong-Sheng Wang, Mario Medvedovic, John N. Lorenz, Gary E. Shull
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a36ff633f7eb4c8c93650c8f1bfceaa9
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spelling	oai:doaj.org-article:a36ff633f7eb4c8c93650c8f1bfceaa92021-12-02T16:06:07ZRNA SEQ Analysis Indicates that the AE3 Cl−/HCO3 − Exchanger Contributes to Active Transport-Mediated CO2 Disposal in Heart10.1038/s41598-017-07585-y2045-2322https://doaj.org/article/a36ff633f7eb4c8c93650c8f1bfceaa92017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07585-yhttps://doaj.org/toc/2045-2322Abstract Loss of the AE3 Cl−/HCO3 − exchanger (Slc4a3) in mice causes an impaired cardiac force-frequency response and heart failure under some conditions but the mechanisms are not known. To better understand the functions of AE3, we performed RNA Seq analysis of AE3-null and wild-type mouse hearts and evaluated the data with respect to three hypotheses (CO2 disposal, facilitation of Na+-loading, and recovery from an alkaline load) that have been proposed for its physiological functions. Gene Ontology and PubMatrix analyses of differentially expressed genes revealed a hypoxia response and changes in vasodilation and angiogenesis genes that strongly support the CO2 disposal hypothesis. Differential expression of energy metabolism genes, which indicated increased glucose utilization and decreased fatty acid utilization, were consistent with adaptive responses to perturbations of O2/CO2 balance in AE3-null myocytes. Given that the myocardium is an obligate aerobic tissue and consumes large amounts of O2, the data suggest that loss of AE3, which has the potential to extrude CO2 in the form of HCO3 −, impairs O2/CO2 balance in cardiac myocytes. These results support a model in which the AE3 Cl−/HCO3 − exchanger, coupled with parallel Cl− and H+-extrusion mechanisms and extracellular carbonic anhydrase, is responsible for active transport-mediated disposal of CO2.Kanimozhi VairamaniHong-Sheng WangMario MedvedovicJohn N. LorenzGary E. ShullNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-16 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Kanimozhi Vairamani Hong-Sheng Wang Mario Medvedovic John N. Lorenz Gary E. Shull RNA SEQ Analysis Indicates that the AE3 Cl−/HCO3 − Exchanger Contributes to Active Transport-Mediated CO2 Disposal in Heart
description	Abstract Loss of the AE3 Cl−/HCO3 − exchanger (Slc4a3) in mice causes an impaired cardiac force-frequency response and heart failure under some conditions but the mechanisms are not known. To better understand the functions of AE3, we performed RNA Seq analysis of AE3-null and wild-type mouse hearts and evaluated the data with respect to three hypotheses (CO2 disposal, facilitation of Na+-loading, and recovery from an alkaline load) that have been proposed for its physiological functions. Gene Ontology and PubMatrix analyses of differentially expressed genes revealed a hypoxia response and changes in vasodilation and angiogenesis genes that strongly support the CO2 disposal hypothesis. Differential expression of energy metabolism genes, which indicated increased glucose utilization and decreased fatty acid utilization, were consistent with adaptive responses to perturbations of O2/CO2 balance in AE3-null myocytes. Given that the myocardium is an obligate aerobic tissue and consumes large amounts of O2, the data suggest that loss of AE3, which has the potential to extrude CO2 in the form of HCO3 −, impairs O2/CO2 balance in cardiac myocytes. These results support a model in which the AE3 Cl−/HCO3 − exchanger, coupled with parallel Cl− and H+-extrusion mechanisms and extracellular carbonic anhydrase, is responsible for active transport-mediated disposal of CO2.
format	article
author	Kanimozhi Vairamani Hong-Sheng Wang Mario Medvedovic John N. Lorenz Gary E. Shull
author_facet	Kanimozhi Vairamani Hong-Sheng Wang Mario Medvedovic John N. Lorenz Gary E. Shull
author_sort	Kanimozhi Vairamani
title	RNA SEQ Analysis Indicates that the AE3 Cl−/HCO3 − Exchanger Contributes to Active Transport-Mediated CO2 Disposal in Heart
title_short	RNA SEQ Analysis Indicates that the AE3 Cl−/HCO3 − Exchanger Contributes to Active Transport-Mediated CO2 Disposal in Heart
title_full	RNA SEQ Analysis Indicates that the AE3 Cl−/HCO3 − Exchanger Contributes to Active Transport-Mediated CO2 Disposal in Heart
title_fullStr	RNA SEQ Analysis Indicates that the AE3 Cl−/HCO3 − Exchanger Contributes to Active Transport-Mediated CO2 Disposal in Heart
title_full_unstemmed	RNA SEQ Analysis Indicates that the AE3 Cl−/HCO3 − Exchanger Contributes to Active Transport-Mediated CO2 Disposal in Heart
title_sort	rna seq analysis indicates that the ae3 cl−/hco3 − exchanger contributes to active transport-mediated co2 disposal in heart
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/a36ff633f7eb4c8c93650c8f1bfceaa9
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RNA SEQ Analysis Indicates that the AE3 Cl−/HCO3 − Exchanger Contributes to Active Transport-Mediated CO2 Disposal in Heart

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