Mitochondrial content is preserved throughout disease progression in the mdx mouse model of Duchenne muscular dystrophy, regardless of taurine supplementation
Mitochondrial dysfunction is a pathological feature of Duchenne muscular dystrophy (DMD), a debilitating and fatal neuromuscular disorder characterized by progressive muscle wasting and weakness. Mitochondria are a source of cellular ATP involved in Ca regulation and apoptotic signaling. Amelioratin...
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Veröffentlicht in: | American Journal of Physiology: Cell Physiology 2018-04, Vol.314 (4), p.C483-C491 |
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description | Mitochondrial dysfunction is a pathological feature of Duchenne muscular dystrophy (DMD), a debilitating and fatal neuromuscular disorder characterized by progressive muscle wasting and weakness. Mitochondria are a source of cellular ATP involved in Ca
regulation and apoptotic signaling. Ameliorating aberrant mitochondrial function has therapeutic potential for reducing DMD disease severity. The dystrophic mdx mouse exhibits peak muscle damage at 21-28 days, which stabilizes after 8 wk. The amino acid taurine is implicated in mitochondrial health and function, with endogenous concentrations low when measured during the cycle of peak muscle damage in mdx mice. Using whole soleus and extensor digitorum longus (EDL) muscle homogenates from 28- and 70-day mdx mice, we found that there was no change in native state mitochondrial complexes using blue native-PAGE. NADH:ubiquinone oxidotreductase subunit-A9 (NDUFA9) protein abundance was lower in soleus muscle of 28- and 70-day mdx mice and EDL muscle of 70-day mdx mice compared with same muscles in WT (C57/BL10ScSn) animals. There were age-dependent increases in both NDUFA9 protein abundance and citrate synthase activity in soleus muscles of mdx and wild-type mice. There was no change in abundances of mitochondrial dynamics proteins mitofusin 2 (Mfn2) and mitochondrial dynamics protein 49 (MiD49). Taurine administration essentially did not affect any measurements of mitochondria. Collectively, these findings suggest mitochondrial content and dynamics are not reduced in the mdx mouse regardless of disease severity. We also elucidate that taurine affords no significant benefit to mitochondrial content or dynamics in the mdx mouse at either 28 or 70 days. |
doi_str_mv | 10.1152/ajpcell.00046.2017 |
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regulation and apoptotic signaling. Ameliorating aberrant mitochondrial function has therapeutic potential for reducing DMD disease severity. The dystrophic mdx mouse exhibits peak muscle damage at 21-28 days, which stabilizes after 8 wk. The amino acid taurine is implicated in mitochondrial health and function, with endogenous concentrations low when measured during the cycle of peak muscle damage in mdx mice. Using whole soleus and extensor digitorum longus (EDL) muscle homogenates from 28- and 70-day mdx mice, we found that there was no change in native state mitochondrial complexes using blue native-PAGE. NADH:ubiquinone oxidotreductase subunit-A9 (NDUFA9) protein abundance was lower in soleus muscle of 28- and 70-day mdx mice and EDL muscle of 70-day mdx mice compared with same muscles in WT (C57/BL10ScSn) animals. There were age-dependent increases in both NDUFA9 protein abundance and citrate synthase activity in soleus muscles of mdx and wild-type mice. There was no change in abundances of mitochondrial dynamics proteins mitofusin 2 (Mfn2) and mitochondrial dynamics protein 49 (MiD49). Taurine administration essentially did not affect any measurements of mitochondria. Collectively, these findings suggest mitochondrial content and dynamics are not reduced in the mdx mouse regardless of disease severity. We also elucidate that taurine affords no significant benefit to mitochondrial content or dynamics in the mdx mouse at either 28 or 70 days.</description><subject>Animals</subject><subject>Citrate (si)-Synthase - metabolism</subject><subject>Dietary Supplements</subject><subject>Disease Models, Animal</subject><subject>Disease Progression</subject><subject>Electron Transport Complex I - metabolism</subject><subject>Electron Transport Complex IV - metabolism</subject><subject>GTP Phosphohydrolases - metabolism</subject><subject>Male</subject><subject>Membrane Proteins - metabolism</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Inbred mdx</subject><subject>Mitochondria, Muscle - drug effects</subject><subject>Mitochondria, Muscle - metabolism</subject><subject>Mitochondria, Muscle - pathology</subject><subject>Mitochondrial Dynamics - drug effects</subject><subject>Mitochondrial Proteins - metabolism</subject><subject>Muscle, Skeletal - drug effects</subject><subject>Muscle, Skeletal - metabolism</subject><subject>Muscle, Skeletal - pathology</subject><subject>Muscular Dystrophy, Duchenne - drug therapy</subject><subject>Muscular Dystrophy, Duchenne - genetics</subject><subject>Muscular Dystrophy, Duchenne - metabolism</subject><subject>Muscular Dystrophy, Duchenne - pathology</subject><subject>Taurine - pharmacology</subject><subject>Time Factors</subject><issn>0363-6143</issn><issn>1522-1563</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9kUtP3DAUha2qqDPQ_oEuKi-7aAY_Mk68rKA8JBAbuo4c-2biURKnfiDmz_BbcWDK6ko-3zm61weh75RsKN2yc7WfNQzDhhBSig0jtPqE1llgBd0K_hmtCRe8ELTkK3Qawn7hmJBf0IpJvqUl5Wv0cm-j072bjLdqwNpNEaaIbcCzhwD-CQyOvXdp17sUsbEBVIAsul3Wg3UTtlMmAI_mGY8uZXF0BgbsOnyZdA_TlF9S0GlQHptDiN7N_eEX9rBT3gw5ZEGjSt5mMqR5HmDMO6iYw7-ik04NAb4d5xn6e_Xn8eKmuHu4vr34fVdoXlaxEELztjNtLYFoY7giQCmDToiqli2rFVSccVmxmlDWCllXohWEkVKWbQu84mfo53tuPuxfghCb0Yblc9UE-aaGylpus60sM8reUe1dCB66ZvZ2VP7QUNIsvTTHXpq3Xpqll2z6ccxP7Qjmw_K_CP4K2e6Paw</recordid><startdate>20180401</startdate><enddate>20180401</enddate><creator>Barker, Robert G</creator><creator>Wyckelsma, Victoria L</creator><creator>Xu, Hongyang</creator><creator>Murphy, Robyn M</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-3697-589X</orcidid></search><sort><creationdate>20180401</creationdate><title>Mitochondrial content is preserved throughout disease progression in the mdx mouse model of Duchenne muscular dystrophy, regardless of taurine supplementation</title><author>Barker, Robert G ; Wyckelsma, Victoria L ; Xu, Hongyang ; Murphy, Robyn M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c347t-66c3bfdb89e0cdd3a0e112ef66789b28ae73239728012b69876b6020494bbe373</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Animals</topic><topic>Citrate (si)-Synthase - metabolism</topic><topic>Dietary Supplements</topic><topic>Disease Models, Animal</topic><topic>Disease Progression</topic><topic>Electron Transport Complex I - metabolism</topic><topic>Electron Transport Complex IV - metabolism</topic><topic>GTP Phosphohydrolases - metabolism</topic><topic>Male</topic><topic>Membrane Proteins - metabolism</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Inbred mdx</topic><topic>Mitochondria, Muscle - drug effects</topic><topic>Mitochondria, Muscle - metabolism</topic><topic>Mitochondria, Muscle - pathology</topic><topic>Mitochondrial Dynamics - drug effects</topic><topic>Mitochondrial Proteins - metabolism</topic><topic>Muscle, Skeletal - drug effects</topic><topic>Muscle, Skeletal - metabolism</topic><topic>Muscle, Skeletal - pathology</topic><topic>Muscular Dystrophy, Duchenne - drug therapy</topic><topic>Muscular Dystrophy, Duchenne - genetics</topic><topic>Muscular Dystrophy, Duchenne - metabolism</topic><topic>Muscular Dystrophy, Duchenne - pathology</topic><topic>Taurine - pharmacology</topic><topic>Time Factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Barker, Robert G</creatorcontrib><creatorcontrib>Wyckelsma, Victoria L</creatorcontrib><creatorcontrib>Xu, Hongyang</creatorcontrib><creatorcontrib>Murphy, Robyn M</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>American Journal of Physiology: Cell Physiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Barker, Robert G</au><au>Wyckelsma, Victoria L</au><au>Xu, Hongyang</au><au>Murphy, Robyn M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Mitochondrial content is preserved throughout disease progression in the mdx mouse model of Duchenne muscular dystrophy, regardless of taurine supplementation</atitle><jtitle>American Journal of Physiology: Cell Physiology</jtitle><addtitle>Am J Physiol Cell Physiol</addtitle><date>2018-04-01</date><risdate>2018</risdate><volume>314</volume><issue>4</issue><spage>C483</spage><epage>C491</epage><pages>C483-C491</pages><issn>0363-6143</issn><eissn>1522-1563</eissn><abstract>Mitochondrial dysfunction is a pathological feature of Duchenne muscular dystrophy (DMD), a debilitating and fatal neuromuscular disorder characterized by progressive muscle wasting and weakness. Mitochondria are a source of cellular ATP involved in Ca
regulation and apoptotic signaling. Ameliorating aberrant mitochondrial function has therapeutic potential for reducing DMD disease severity. The dystrophic mdx mouse exhibits peak muscle damage at 21-28 days, which stabilizes after 8 wk. The amino acid taurine is implicated in mitochondrial health and function, with endogenous concentrations low when measured during the cycle of peak muscle damage in mdx mice. Using whole soleus and extensor digitorum longus (EDL) muscle homogenates from 28- and 70-day mdx mice, we found that there was no change in native state mitochondrial complexes using blue native-PAGE. NADH:ubiquinone oxidotreductase subunit-A9 (NDUFA9) protein abundance was lower in soleus muscle of 28- and 70-day mdx mice and EDL muscle of 70-day mdx mice compared with same muscles in WT (C57/BL10ScSn) animals. There were age-dependent increases in both NDUFA9 protein abundance and citrate synthase activity in soleus muscles of mdx and wild-type mice. There was no change in abundances of mitochondrial dynamics proteins mitofusin 2 (Mfn2) and mitochondrial dynamics protein 49 (MiD49). Taurine administration essentially did not affect any measurements of mitochondria. Collectively, these findings suggest mitochondrial content and dynamics are not reduced in the mdx mouse regardless of disease severity. We also elucidate that taurine affords no significant benefit to mitochondrial content or dynamics in the mdx mouse at either 28 or 70 days.</abstract><cop>United States</cop><pmid>29351413</pmid><doi>10.1152/ajpcell.00046.2017</doi><orcidid>https://orcid.org/0000-0003-3697-589X</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Animals Citrate (si)-Synthase - metabolism Dietary Supplements Disease Models, Animal Disease Progression Electron Transport Complex I - metabolism Electron Transport Complex IV - metabolism GTP Phosphohydrolases - metabolism Male Membrane Proteins - metabolism Mice, Inbred C57BL Mice, Inbred mdx Mitochondria, Muscle - drug effects Mitochondria, Muscle - metabolism Mitochondria, Muscle - pathology Mitochondrial Dynamics - drug effects Mitochondrial Proteins - metabolism Muscle, Skeletal - drug effects Muscle, Skeletal - metabolism Muscle, Skeletal - pathology Muscular Dystrophy, Duchenne - drug therapy Muscular Dystrophy, Duchenne - genetics Muscular Dystrophy, Duchenne - metabolism Muscular Dystrophy, Duchenne - pathology Taurine - pharmacology Time Factors |
title | Mitochondrial content is preserved throughout disease progression in the mdx mouse model of Duchenne muscular dystrophy, regardless of taurine supplementation |
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