Epithelial magnesium transport by TRPM6 is essential for prenatal development and adult survival.

Autor:	Chubanov V; Walther-Straub Institute of Pharmacology and Toxicology, Ludwig Maximilian University of Munich, Munich, Germany., Ferioli S; Walther-Straub Institute of Pharmacology and Toxicology, Ludwig Maximilian University of Munich, Munich, Germany., Wisnowsky A; Walther-Straub Institute of Pharmacology and Toxicology, Ludwig Maximilian University of Munich, Munich, Germany., Simmons DG; School of Biomedical Sciences, The University of Queensland, Brisbane, Australia., Leitzinger C; Institute of Molecular Toxicology and Pharmacology, Helmholtz Zentrum Munich, Neuherberg, Germany., Einer C; Institute of Molecular Toxicology and Pharmacology, Helmholtz Zentrum Munich, Neuherberg, Germany., Jonas W; Department of Experimental Diabetology, German Institute of Human Nutrition, Potsdam-Rehbruecke, Germany.; German Center for Diabetes Research, Munich, Germany., Shymkiv Y; Princeton Institute of Life Sciences, Princeton, United States., Bartsch H; Institute of Pathology, Ludwig Maximilian University of Munich, Munich, Germany., Braun A; Rudolf Virchow Center for Experimental Biomedicine, University of Würzburg, Würzburg, Germany.; Department of Vascular Medicine, University Hospital Würzburg, Würzburg, Germany., Akdogan B; Walther-Straub Institute of Pharmacology and Toxicology, Ludwig Maximilian University of Munich, Munich, Germany., Mittermeier L; Walther-Straub Institute of Pharmacology and Toxicology, Ludwig Maximilian University of Munich, Munich, Germany., Sytik L; Walther-Straub Institute of Pharmacology and Toxicology, Ludwig Maximilian University of Munich, Munich, Germany., Torben F; Genome Analysis Center, Institute of Experimental Genetics, Helmholtz Zentrum Munich, Neuherberg, Germany., Jurinovic V; Institute for Medical Informatics, Biometry and Epidemiology, Ludwig Maximilian University of Munich, Munich, Germany., van der Vorst EP; Institute for Cardiovascular Prevention, Ludwig Maximilian University of Munich, Munich, Germany., Weber C; Institute for Cardiovascular Prevention, Ludwig Maximilian University of Munich, Munich, Germany.; German Centre for Cardiovascular Research, Munich Heart Alliance, Munich, Germany., Yildirim ÖA; Comprehensive Pneumology Center, Institute of Lung Biology and Disease, Helmholtz Zentrum Munich, Neuherberg, Germany.; German Center for Lung Research, Munich, Germany., Sotlar K; Institute of Pathology, Ludwig Maximilian University of Munich, Munich, Germany., Schürmann A; Department of Experimental Diabetology, German Institute of Human Nutrition, Potsdam-Rehbruecke, Germany.; German Center for Diabetes Research, Munich, Germany., Zierler S; Walther-Straub Institute of Pharmacology and Toxicology, Ludwig Maximilian University of Munich, Munich, Germany., Zischka H; Institute of Molecular Toxicology and Pharmacology, Helmholtz Zentrum Munich, Neuherberg, Germany., Ryazanov AG; Princeton Institute of Life Sciences, Princeton, United States.; Department of Cellular and Molecular Pharmacology, Rutgers Robert Wood Johnson Medical School, Piscataway, United States., Gudermann T; Walther-Straub Institute of Pharmacology and Toxicology, Ludwig Maximilian University of Munich, Munich, Germany.; German Centre for Cardiovascular Research, Munich Heart Alliance, Munich, Germany.; Comprehensive Pneumology Center Munich, German Center for Lung Research, Munich, Germany.
Jazyk:	angličtina
Zdroj:	ELife [Elife] 2016 Dec 19; Vol. 5. Date of Electronic Publication: 2016 Dec 19.
DOI:	10.7554/eLife.20914
Abstrakt:	Mg 2+ regulates many physiological processes and signalling pathways. However, little is known about the mechanisms underlying the organismal balance of Mg 2+ . Capitalizing on a set of newly generated mouse models, we provide an integrated mechanistic model of the regulation of organismal Mg 2+ balance during prenatal development and in adult mice by the ion channel TRPM6. We show that TRPM6 activity in the placenta and yolk sac is essential for embryonic development. In adult mice, TRPM6 is required in the intestine to maintain organismal Mg 2+ balance, but is dispensable in the kidney. Trpm6 inactivation in adult mice leads to a shortened lifespan, growth deficit and metabolic alterations indicative of impaired energy balance. Dietary Mg 2+ supplementation not only rescues all phenotypes displayed by Trpm6 -deficient adult mice, but also may extend the lifespan of wildtype mice. Hence, maintenance of organismal Mg 2+ balance by TRPM6 is crucial for prenatal development and survival to adulthood. Competing Interests: The authors declare that no competing interests exist.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu