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Combined Omics Reveals That Disruption of the Selenocysteine Lyase Gene Affects Amino Acid Pathways in Mice

Selenium is a nonmetal trace element that is critical for several redox reactions and utilized to produce the amino acid selenocysteine (Sec), which can be incorporated into selenoproteins. Selenocysteine lyase (SCL) is an enzyme which decomposes Sec into selenide and alanine, releasing the selenide...

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Autores principales: Seale, Lucia A., Khadka, Vedbar S., Menor, Mark, Xie, Guoxiang, Watanabe, Ligia M., Sasuclark, Alexandru, Guirguis, Kyrillos, Ha, Herena Y., Hashimoto, Ann C., Peplowska, Karolina, Tiirikainen, Maarit, Jia, Wei, Berry, Marla J., Deng, Youping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6893568/
https://www.ncbi.nlm.nih.gov/pubmed/31717805
http://dx.doi.org/10.3390/nu11112584
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author Seale, Lucia A.
Khadka, Vedbar S.
Menor, Mark
Xie, Guoxiang
Watanabe, Ligia M.
Sasuclark, Alexandru
Guirguis, Kyrillos
Ha, Herena Y.
Hashimoto, Ann C.
Peplowska, Karolina
Tiirikainen, Maarit
Jia, Wei
Berry, Marla J.
Deng, Youping
author_facet Seale, Lucia A.
Khadka, Vedbar S.
Menor, Mark
Xie, Guoxiang
Watanabe, Ligia M.
Sasuclark, Alexandru
Guirguis, Kyrillos
Ha, Herena Y.
Hashimoto, Ann C.
Peplowska, Karolina
Tiirikainen, Maarit
Jia, Wei
Berry, Marla J.
Deng, Youping
author_sort Seale, Lucia A.
collection PubMed
description Selenium is a nonmetal trace element that is critical for several redox reactions and utilized to produce the amino acid selenocysteine (Sec), which can be incorporated into selenoproteins. Selenocysteine lyase (SCL) is an enzyme which decomposes Sec into selenide and alanine, releasing the selenide to be further utilized to synthesize new selenoproteins. Disruption of the selenocysteine lyase gene (Scly) in mice (Scly(−/−) or Scly KO) led to obesity with dyslipidemia, hyperinsulinemia, glucose intolerance and lipid accumulation in the hepatocytes. As the liver is a central regulator of glucose and lipid homeostasis, as well as selenium metabolism, we aimed to pinpoint hepatic molecular pathways affected by the Scly gene disruption. Using RNA sequencing and metabolomics, we identified differentially expressed genes and metabolites in the livers of Scly KO mice. Integrated omics revealed that biological pathways related to amino acid metabolism, particularly alanine and glycine metabolism, were affected in the liver by disruption of Scly in mice with selenium adequacy. We further confirmed that hepatic glycine levels are elevated in male, but not in female, Scly KO mice. In conclusion, our results reveal that Scly participates in the modulation of hepatic amino acid metabolic pathways.
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spelling pubmed-68935682019-12-23 Combined Omics Reveals That Disruption of the Selenocysteine Lyase Gene Affects Amino Acid Pathways in Mice Seale, Lucia A. Khadka, Vedbar S. Menor, Mark Xie, Guoxiang Watanabe, Ligia M. Sasuclark, Alexandru Guirguis, Kyrillos Ha, Herena Y. Hashimoto, Ann C. Peplowska, Karolina Tiirikainen, Maarit Jia, Wei Berry, Marla J. Deng, Youping Nutrients Article Selenium is a nonmetal trace element that is critical for several redox reactions and utilized to produce the amino acid selenocysteine (Sec), which can be incorporated into selenoproteins. Selenocysteine lyase (SCL) is an enzyme which decomposes Sec into selenide and alanine, releasing the selenide to be further utilized to synthesize new selenoproteins. Disruption of the selenocysteine lyase gene (Scly) in mice (Scly(−/−) or Scly KO) led to obesity with dyslipidemia, hyperinsulinemia, glucose intolerance and lipid accumulation in the hepatocytes. As the liver is a central regulator of glucose and lipid homeostasis, as well as selenium metabolism, we aimed to pinpoint hepatic molecular pathways affected by the Scly gene disruption. Using RNA sequencing and metabolomics, we identified differentially expressed genes and metabolites in the livers of Scly KO mice. Integrated omics revealed that biological pathways related to amino acid metabolism, particularly alanine and glycine metabolism, were affected in the liver by disruption of Scly in mice with selenium adequacy. We further confirmed that hepatic glycine levels are elevated in male, but not in female, Scly KO mice. In conclusion, our results reveal that Scly participates in the modulation of hepatic amino acid metabolic pathways. MDPI 2019-10-26 /pmc/articles/PMC6893568/ /pubmed/31717805 http://dx.doi.org/10.3390/nu11112584 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Seale, Lucia A.
Khadka, Vedbar S.
Menor, Mark
Xie, Guoxiang
Watanabe, Ligia M.
Sasuclark, Alexandru
Guirguis, Kyrillos
Ha, Herena Y.
Hashimoto, Ann C.
Peplowska, Karolina
Tiirikainen, Maarit
Jia, Wei
Berry, Marla J.
Deng, Youping
Combined Omics Reveals That Disruption of the Selenocysteine Lyase Gene Affects Amino Acid Pathways in Mice
title Combined Omics Reveals That Disruption of the Selenocysteine Lyase Gene Affects Amino Acid Pathways in Mice
title_full Combined Omics Reveals That Disruption of the Selenocysteine Lyase Gene Affects Amino Acid Pathways in Mice
title_fullStr Combined Omics Reveals That Disruption of the Selenocysteine Lyase Gene Affects Amino Acid Pathways in Mice
title_full_unstemmed Combined Omics Reveals That Disruption of the Selenocysteine Lyase Gene Affects Amino Acid Pathways in Mice
title_short Combined Omics Reveals That Disruption of the Selenocysteine Lyase Gene Affects Amino Acid Pathways in Mice
title_sort combined omics reveals that disruption of the selenocysteine lyase gene affects amino acid pathways in mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6893568/
https://www.ncbi.nlm.nih.gov/pubmed/31717805
http://dx.doi.org/10.3390/nu11112584
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