Large-scaled metabolic profiling of human dermal fibroblasts derived from pseudoxanthoma elasticum patients and healthy controls.

Mutations in the ABC transporter ABCC6 were recently identified as cause of Pseudoxanthoma elasticum (PXE), a rare genetic disorder characterized by progressive mineralization of elastic fibers. We used an untargeted metabolic approach to identify biochemical differences between human dermal fibrobl...

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Autores principales:	Patricia Kuzaj, Joachim Kuhn, Ryan D Michalek, Edward D Karoly, Isabel Faust, Mareike Dabisch-Ruthe, Cornelius Knabbe, Doris Hendig
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2e0962879a3d4336ac5b4518d8b8c4e1
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spelling	oai:doaj.org-article:2e0962879a3d4336ac5b4518d8b8c4e12021-11-25T05:58:54ZLarge-scaled metabolic profiling of human dermal fibroblasts derived from pseudoxanthoma elasticum patients and healthy controls.1932-620310.1371/journal.pone.0108336https://doaj.org/article/2e0962879a3d4336ac5b4518d8b8c4e12014-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0108336https://doaj.org/toc/1932-6203Mutations in the ABC transporter ABCC6 were recently identified as cause of Pseudoxanthoma elasticum (PXE), a rare genetic disorder characterized by progressive mineralization of elastic fibers. We used an untargeted metabolic approach to identify biochemical differences between human dermal fibroblasts from healthy controls and PXE patients in an attempt to find a link between ABCC6 deficiency, cellular metabolic alterations and disease pathogenesis. 358 compounds were identified by mass spectrometry covering lipids, amino acids, peptides, carbohydrates, nucleotides, vitamins and cofactors, xenobiotics and energy metabolites. We found substantial differences in glycerophospholipid composition, leucine dipeptides, and polypeptides as well as alterations in pantothenate and guanine metabolism to be significantly associated with PXE pathogenesis. These findings can be linked to extracellular matrix remodeling and increased oxidative stress, which reflect characteristic hallmarks of PXE. Our study could facilitate a better understanding of biochemical pathways involved in soft tissue mineralization.Patricia KuzajJoachim KuhnRyan D MichalekEdward D KarolyIsabel FaustMareike Dabisch-RutheCornelius KnabbeDoris HendigPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 9, p e108336 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Patricia Kuzaj Joachim Kuhn Ryan D Michalek Edward D Karoly Isabel Faust Mareike Dabisch-Ruthe Cornelius Knabbe Doris Hendig Large-scaled metabolic profiling of human dermal fibroblasts derived from pseudoxanthoma elasticum patients and healthy controls.
description	Mutations in the ABC transporter ABCC6 were recently identified as cause of Pseudoxanthoma elasticum (PXE), a rare genetic disorder characterized by progressive mineralization of elastic fibers. We used an untargeted metabolic approach to identify biochemical differences between human dermal fibroblasts from healthy controls and PXE patients in an attempt to find a link between ABCC6 deficiency, cellular metabolic alterations and disease pathogenesis. 358 compounds were identified by mass spectrometry covering lipids, amino acids, peptides, carbohydrates, nucleotides, vitamins and cofactors, xenobiotics and energy metabolites. We found substantial differences in glycerophospholipid composition, leucine dipeptides, and polypeptides as well as alterations in pantothenate and guanine metabolism to be significantly associated with PXE pathogenesis. These findings can be linked to extracellular matrix remodeling and increased oxidative stress, which reflect characteristic hallmarks of PXE. Our study could facilitate a better understanding of biochemical pathways involved in soft tissue mineralization.
format	article
author	Patricia Kuzaj Joachim Kuhn Ryan D Michalek Edward D Karoly Isabel Faust Mareike Dabisch-Ruthe Cornelius Knabbe Doris Hendig
author_facet	Patricia Kuzaj Joachim Kuhn Ryan D Michalek Edward D Karoly Isabel Faust Mareike Dabisch-Ruthe Cornelius Knabbe Doris Hendig
author_sort	Patricia Kuzaj
title	Large-scaled metabolic profiling of human dermal fibroblasts derived from pseudoxanthoma elasticum patients and healthy controls.
title_short	Large-scaled metabolic profiling of human dermal fibroblasts derived from pseudoxanthoma elasticum patients and healthy controls.
title_full	Large-scaled metabolic profiling of human dermal fibroblasts derived from pseudoxanthoma elasticum patients and healthy controls.
title_fullStr	Large-scaled metabolic profiling of human dermal fibroblasts derived from pseudoxanthoma elasticum patients and healthy controls.
title_full_unstemmed	Large-scaled metabolic profiling of human dermal fibroblasts derived from pseudoxanthoma elasticum patients and healthy controls.
title_sort	large-scaled metabolic profiling of human dermal fibroblasts derived from pseudoxanthoma elasticum patients and healthy controls.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/2e0962879a3d4336ac5b4518d8b8c4e1
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Large-scaled metabolic profiling of human dermal fibroblasts derived from pseudoxanthoma elasticum patients and healthy controls.

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