Proteome Profiling of the Dystrophic <i>mdx</i> Mice Diaphragm
<i>Mdx</i> mice with a spontaneous mutation in exon 23 of the <i>Dmd</i> gene represent the most common model to investigate the pathophysiology of Duchenne muscular dystrophy (DMD). The disease, caused by the lack of functional dystrophin, is characterized by irreversible im...
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MDPI AG
2023-11-01
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| Series: | Biomolecules |
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| author | Olga Mucha Małgorzata Myszka Paulina Podkalicka Bianka Świderska Agata Malinowska Józef Dulak Agnieszka Łoboda |
| author_facet | Olga Mucha Małgorzata Myszka Paulina Podkalicka Bianka Świderska Agata Malinowska Józef Dulak Agnieszka Łoboda |
| author_sort | Olga Mucha |
| collection | DOAJ |
| description | <i>Mdx</i> mice with a spontaneous mutation in exon 23 of the <i>Dmd</i> gene represent the most common model to investigate the pathophysiology of Duchenne muscular dystrophy (DMD). The disease, caused by the lack of functional dystrophin, is characterized by irreversible impairment of muscle functions, with the diaphragm affected earlier and more severely than other skeletal muscles. We applied a label-free (LF) method and the more thorough tandem mass tag (TMT)-based method to analyze differentially expressed proteins in the diaphragm of 6-week-old <i>mdx</i> mice. The comparison of both methods revealed 88 commonly changed proteins. A more in-depth analysis of the TMT-based method showed 953 significantly changed proteins, with 867 increased and 86 decreased in dystrophic animals (<i>q</i>-value < 0.05, fold-change threshold: 1.5). Consequently, several dysregulated processes were demonstrated, including the immune response, fibrosis, translation, and programmed cell death. Interestingly, in the dystrophic diaphragm, we found a significant decrease in the expression of enzymes generating hydrogen sulfide (H<sub>2</sub>S), suggesting that alterations in the metabolism of this gaseous mediator could modulate DMD progression, which could be a potential target for pharmacological intervention. |
| first_indexed | 2024-03-09T16:58:53Z |
| format | Article |
| id | doaj.art-b5a527238d524efe87466f14c2ea7a38 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-09T16:58:53Z |
| publishDate | 2023-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-b5a527238d524efe87466f14c2ea7a382023-11-24T14:32:06ZengMDPI AGBiomolecules2218-273X2023-11-011311164810.3390/biom13111648Proteome Profiling of the Dystrophic <i>mdx</i> Mice DiaphragmOlga Mucha0Małgorzata Myszka1Paulina Podkalicka2Bianka Świderska3Agata Malinowska4Józef Dulak5Agnieszka Łoboda6Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University in Krakow, Gronostajowa 7 Street, 30-387 Kraków, PolandDepartment of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University in Krakow, Gronostajowa 7 Street, 30-387 Kraków, PolandDepartment of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University in Krakow, Gronostajowa 7 Street, 30-387 Kraków, PolandMass Spectrometry Laboratory, Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawińskiego 5a Street, 02-106 Warsaw, PolandMass Spectrometry Laboratory, Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawińskiego 5a Street, 02-106 Warsaw, PolandDepartment of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University in Krakow, Gronostajowa 7 Street, 30-387 Kraków, PolandDepartment of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University in Krakow, Gronostajowa 7 Street, 30-387 Kraków, Poland<i>Mdx</i> mice with a spontaneous mutation in exon 23 of the <i>Dmd</i> gene represent the most common model to investigate the pathophysiology of Duchenne muscular dystrophy (DMD). The disease, caused by the lack of functional dystrophin, is characterized by irreversible impairment of muscle functions, with the diaphragm affected earlier and more severely than other skeletal muscles. We applied a label-free (LF) method and the more thorough tandem mass tag (TMT)-based method to analyze differentially expressed proteins in the diaphragm of 6-week-old <i>mdx</i> mice. The comparison of both methods revealed 88 commonly changed proteins. A more in-depth analysis of the TMT-based method showed 953 significantly changed proteins, with 867 increased and 86 decreased in dystrophic animals (<i>q</i>-value < 0.05, fold-change threshold: 1.5). Consequently, several dysregulated processes were demonstrated, including the immune response, fibrosis, translation, and programmed cell death. Interestingly, in the dystrophic diaphragm, we found a significant decrease in the expression of enzymes generating hydrogen sulfide (H<sub>2</sub>S), suggesting that alterations in the metabolism of this gaseous mediator could modulate DMD progression, which could be a potential target for pharmacological intervention.https://www.mdpi.com/2218-273X/13/11/1648aquaporin 4Duchenne muscular dystrophyhydrogen sulfide<i>mdx</i> diaphragmCTHCBS |
| spellingShingle | Olga Mucha Małgorzata Myszka Paulina Podkalicka Bianka Świderska Agata Malinowska Józef Dulak Agnieszka Łoboda Proteome Profiling of the Dystrophic <i>mdx</i> Mice Diaphragm Biomolecules aquaporin 4 Duchenne muscular dystrophy hydrogen sulfide <i>mdx</i> diaphragm CTH CBS |
| title | Proteome Profiling of the Dystrophic <i>mdx</i> Mice Diaphragm |
| title_full | Proteome Profiling of the Dystrophic <i>mdx</i> Mice Diaphragm |
| title_fullStr | Proteome Profiling of the Dystrophic <i>mdx</i> Mice Diaphragm |
| title_full_unstemmed | Proteome Profiling of the Dystrophic <i>mdx</i> Mice Diaphragm |
| title_short | Proteome Profiling of the Dystrophic <i>mdx</i> Mice Diaphragm |
| title_sort | proteome profiling of the dystrophic i mdx i mice diaphragm |
| topic | aquaporin 4 Duchenne muscular dystrophy hydrogen sulfide <i>mdx</i> diaphragm CTH CBS |
| url | https://www.mdpi.com/2218-273X/13/11/1648 |
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