Thioredoxin Domain Containing 5 Suppression Elicits Serum Amyloid A-Containing High-Density Lipoproteins

Thioredoxin domain containing 5 (TXNDC5) is a protein disulfide isomerase involved in several diseases related to oxidative stress, energy metabolism and cellular inflammation. In a previous manuscript, a negative association between fatty liver development and hepatic <i>Txndc5</i> expr...

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Main Authors: Javier Sánchez-Marco, Roberto Martínez-Beamonte, Alicia De Diego, Tania Herrero-Continente, Cristina Barranquero, Carmen Arnal, Joaquín Surra, María A. Navarro, Jesús Osada
Format: Article
Language:English
Published: MDPI AG 2022-03-01
Series:Biomedicines
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Online Access:https://www.mdpi.com/2227-9059/10/3/709
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author Javier Sánchez-Marco
Roberto Martínez-Beamonte
Alicia De Diego
Tania Herrero-Continente
Cristina Barranquero
Carmen Arnal
Joaquín Surra
María A. Navarro
Jesús Osada
author_facet Javier Sánchez-Marco
Roberto Martínez-Beamonte
Alicia De Diego
Tania Herrero-Continente
Cristina Barranquero
Carmen Arnal
Joaquín Surra
María A. Navarro
Jesús Osada
author_sort Javier Sánchez-Marco
collection DOAJ
description Thioredoxin domain containing 5 (TXNDC5) is a protein disulfide isomerase involved in several diseases related to oxidative stress, energy metabolism and cellular inflammation. In a previous manuscript, a negative association between fatty liver development and hepatic <i>Txndc5</i> expression was observed. To study the role of TXNDC5 in the liver, we generated <i>Txndc5</i>-deficient mice. The absence of the protein caused an increased metabolic need to gain weight along with a bigger and fatter liver. RNAseq was performed to elucidate the putative mechanisms, showing a substantial liver overexpression of serum amyloid genes (<i>Saa1</i>, <i>Saa2</i>) with no changes in hepatic protein, but discrete plasma augmentation by the gene inactivation. Higher levels of malonyldialdehyde, apolipoprotein A1 and platelet activating factor-aryl esterase activity were also found in serum from <i>Txndc5</i>-deficient mice. However, no difference in the distribution of high-density lipoproteins (HDL)-mayor components and SAA was found between groups, and even the reactive oxygen species decreased in HDL coming from <i>Txndc5</i>-deficient mice. These results confirm the relation of this gene with hepatic steatosis and with a fasting metabolic derive remedying an acute phase response. Likewise, they pose a new role in modulating the nature of HDL particles, and SAA-containing HDL particles are not particularly oxidized.
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spelling doaj.art-9b6b829917614855befc9c931295db842023-11-30T20:53:29ZengMDPI AGBiomedicines2227-90592022-03-0110370910.3390/biomedicines10030709Thioredoxin Domain Containing 5 Suppression Elicits Serum Amyloid A-Containing High-Density LipoproteinsJavier Sánchez-Marco0Roberto Martínez-Beamonte1Alicia De Diego2Tania Herrero-Continente3Cristina Barranquero4Carmen Arnal5Joaquín Surra6María A. Navarro7Jesús Osada8Departamento de Bioquímica y Biología Molecular y Celular, Facultad de Veterinaria, Instituto de Investigación Sanitaria de Aragón-Universidad de Zaragoza, E-50013 Zaragoza, SpainDepartamento de Bioquímica y Biología Molecular y Celular, Facultad de Veterinaria, Instituto de Investigación Sanitaria de Aragón-Universidad de Zaragoza, E-50013 Zaragoza, SpainInstituto de Investigación Sanitaria de Aragón (IISA), Universidad de Zaragoza, E-50013 Zaragoza, SpainDepartamento de Bioquímica y Biología Molecular y Celular, Facultad de Veterinaria, Instituto de Investigación Sanitaria de Aragón-Universidad de Zaragoza, E-50013 Zaragoza, SpainInstituto Agroalimentario de Aragón, CITA-Universidad de Zaragoza, E-50013 Zaragoza, SpainInstituto Agroalimentario de Aragón, CITA-Universidad de Zaragoza, E-50013 Zaragoza, SpainInstituto Agroalimentario de Aragón, CITA-Universidad de Zaragoza, E-50013 Zaragoza, SpainDepartamento de Bioquímica y Biología Molecular y Celular, Facultad de Veterinaria, Instituto de Investigación Sanitaria de Aragón-Universidad de Zaragoza, E-50013 Zaragoza, SpainDepartamento de Bioquímica y Biología Molecular y Celular, Facultad de Veterinaria, Instituto de Investigación Sanitaria de Aragón-Universidad de Zaragoza, E-50013 Zaragoza, SpainThioredoxin domain containing 5 (TXNDC5) is a protein disulfide isomerase involved in several diseases related to oxidative stress, energy metabolism and cellular inflammation. In a previous manuscript, a negative association between fatty liver development and hepatic <i>Txndc5</i> expression was observed. To study the role of TXNDC5 in the liver, we generated <i>Txndc5</i>-deficient mice. The absence of the protein caused an increased metabolic need to gain weight along with a bigger and fatter liver. RNAseq was performed to elucidate the putative mechanisms, showing a substantial liver overexpression of serum amyloid genes (<i>Saa1</i>, <i>Saa2</i>) with no changes in hepatic protein, but discrete plasma augmentation by the gene inactivation. Higher levels of malonyldialdehyde, apolipoprotein A1 and platelet activating factor-aryl esterase activity were also found in serum from <i>Txndc5</i>-deficient mice. However, no difference in the distribution of high-density lipoproteins (HDL)-mayor components and SAA was found between groups, and even the reactive oxygen species decreased in HDL coming from <i>Txndc5</i>-deficient mice. These results confirm the relation of this gene with hepatic steatosis and with a fasting metabolic derive remedying an acute phase response. Likewise, they pose a new role in modulating the nature of HDL particles, and SAA-containing HDL particles are not particularly oxidized.https://www.mdpi.com/2227-9059/10/3/709thioredoxin domain containing 5TXNDC5serum amyloidHDLSAA<i>Saa1</i>
spellingShingle Javier Sánchez-Marco
Roberto Martínez-Beamonte
Alicia De Diego
Tania Herrero-Continente
Cristina Barranquero
Carmen Arnal
Joaquín Surra
María A. Navarro
Jesús Osada
Thioredoxin Domain Containing 5 Suppression Elicits Serum Amyloid A-Containing High-Density Lipoproteins
Biomedicines
thioredoxin domain containing 5
TXNDC5
serum amyloid
HDL
SAA
<i>Saa1</i>
title Thioredoxin Domain Containing 5 Suppression Elicits Serum Amyloid A-Containing High-Density Lipoproteins
title_full Thioredoxin Domain Containing 5 Suppression Elicits Serum Amyloid A-Containing High-Density Lipoproteins
title_fullStr Thioredoxin Domain Containing 5 Suppression Elicits Serum Amyloid A-Containing High-Density Lipoproteins
title_full_unstemmed Thioredoxin Domain Containing 5 Suppression Elicits Serum Amyloid A-Containing High-Density Lipoproteins
title_short Thioredoxin Domain Containing 5 Suppression Elicits Serum Amyloid A-Containing High-Density Lipoproteins
title_sort thioredoxin domain containing 5 suppression elicits serum amyloid a containing high density lipoproteins
topic thioredoxin domain containing 5
TXNDC5
serum amyloid
HDL
SAA
<i>Saa1</i>
url https://www.mdpi.com/2227-9059/10/3/709
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