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Alterations in mitochondrial fission, fusion, and mitophagic protein expression in the gastrocnemius of mice after a sciatic nerve transection
ABSTRACT Introduction Paralysis and unloading of skeletal muscle leads to a rapid loss in muscle size, function and oxidative capacity. The reduction in metabolic capability after disuse leads to dysregulation and increased breakdown of mitochondria by mitophagy. Methods Eight‐week‐old C57BL/6 male...
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| Published in: | Muscle & nerve 2018-10, Vol.58 (4), p.592-599 |
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| container_title | Muscle & nerve |
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| creator | Graham, Zachary A. Harlow, Lauren Bauman, William A. Cardozo, Christopher P. |
| description | ABSTRACT
Introduction
Paralysis and unloading of skeletal muscle leads to a rapid loss in muscle size, function and oxidative capacity. The reduction in metabolic capability after disuse leads to dysregulation and increased breakdown of mitochondria by mitophagy.
Methods
Eight‐week‐old C57BL/6 male mice were given a sham surgery or sciatic nerve transection. Animals were euthanized at 7, 14, 21, or 35 days postsurgery. Whole gastrocnemius muscles were isolated from the animal, weighed and used for Western blotting.
Results
Markers of mitochondrial fusion were reduced while fission proteins were elevated following a sciatic nerve transection. There were elevations in phosphorylated unc‐51‐like kinase 1 (ULK1S555) and total expression of Beclin1, and of the mitophagy markers PINK1, p62, and microtubule‐associated proteins 1A/1B light chain 3b (LC3‐II).
Conclusions
Paralysis of the gastrocnemius leads to a progressive elevation in expression of mitochondrial fission and mitophagic proteins. Rehabilitative or pharmaceutical interventions to limit excess mitophagy may be effective therapies to protect paralyzed muscle mass and function. Muscle Nerve 58: 592–599, 2018 |
| doi_str_mv | 10.1002/mus.26197 |
| format | article |
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Introduction
Paralysis and unloading of skeletal muscle leads to a rapid loss in muscle size, function and oxidative capacity. The reduction in metabolic capability after disuse leads to dysregulation and increased breakdown of mitochondria by mitophagy.
Methods
Eight‐week‐old C57BL/6 male mice were given a sham surgery or sciatic nerve transection. Animals were euthanized at 7, 14, 21, or 35 days postsurgery. Whole gastrocnemius muscles were isolated from the animal, weighed and used for Western blotting.
Results
Markers of mitochondrial fusion were reduced while fission proteins were elevated following a sciatic nerve transection. There were elevations in phosphorylated unc‐51‐like kinase 1 (ULK1S555) and total expression of Beclin1, and of the mitophagy markers PINK1, p62, and microtubule‐associated proteins 1A/1B light chain 3b (LC3‐II).
Conclusions
Paralysis of the gastrocnemius leads to a progressive elevation in expression of mitochondrial fission and mitophagic proteins. Rehabilitative or pharmaceutical interventions to limit excess mitophagy may be effective therapies to protect paralyzed muscle mass and function. Muscle Nerve 58: 592–599, 2018</description><identifier>ISSN: 0148-639X</identifier><identifier>EISSN: 1097-4598</identifier><identifier>DOI: 10.1002/mus.26197</identifier><identifier>PMID: 30028528</identifier><language>eng</language><publisher>United States: Wiley Subscription Services, Inc</publisher><subject>Animals ; Autophagy-Related Protein-1 Homolog - metabolism ; Beclin-1 - metabolism ; denervation ; Fission ; fusion ; Fusion protein ; Male ; Markers ; Membrane Proteins - metabolism ; Mice ; Microtubule-Associated Proteins - metabolism ; Mitochondria ; Mitochondrial Dynamics ; Mitochondrial Proteins - metabolism ; Mitophagy ; Muscle Denervation ; Muscle, Skeletal - innervation ; Muscle, Skeletal - metabolism ; Muscle, Skeletal - pathology ; Muscles ; Organ Size ; Paralysis ; Peripheral Nerve Injuries - metabolism ; Phosphoproteins ; Protein Kinases - metabolism ; Proteins ; PTEN-induced putative kinase ; Rodents ; Sciatic nerve ; Sciatic Nerve - injuries ; Skeletal muscle ; Surgery ; Unloading ; Western blotting</subject><ispartof>Muscle & nerve, 2018-10, Vol.58 (4), p.592-599</ispartof><rights>Published 2018. This article is a U.S. Government work and is in the public domain in the USA.</rights><rights>2018 Wiley Periodicals, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4197-8187618f0ff337f1c5ff0a9dc6d88879bb8403239ea3e54041cbe39094f2e7393</citedby><cites>FETCH-LOGICAL-c4197-8187618f0ff337f1c5ff0a9dc6d88879bb8403239ea3e54041cbe39094f2e7393</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30028528$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Graham, Zachary A.</creatorcontrib><creatorcontrib>Harlow, Lauren</creatorcontrib><creatorcontrib>Bauman, William A.</creatorcontrib><creatorcontrib>Cardozo, Christopher P.</creatorcontrib><title>Alterations in mitochondrial fission, fusion, and mitophagic protein expression in the gastrocnemius of mice after a sciatic nerve transection</title><title>Muscle & nerve</title><addtitle>Muscle Nerve</addtitle><description>ABSTRACT
Introduction
Paralysis and unloading of skeletal muscle leads to a rapid loss in muscle size, function and oxidative capacity. The reduction in metabolic capability after disuse leads to dysregulation and increased breakdown of mitochondria by mitophagy.
Methods
Eight‐week‐old C57BL/6 male mice were given a sham surgery or sciatic nerve transection. Animals were euthanized at 7, 14, 21, or 35 days postsurgery. Whole gastrocnemius muscles were isolated from the animal, weighed and used for Western blotting.
Results
Markers of mitochondrial fusion were reduced while fission proteins were elevated following a sciatic nerve transection. There were elevations in phosphorylated unc‐51‐like kinase 1 (ULK1S555) and total expression of Beclin1, and of the mitophagy markers PINK1, p62, and microtubule‐associated proteins 1A/1B light chain 3b (LC3‐II).
Conclusions
Paralysis of the gastrocnemius leads to a progressive elevation in expression of mitochondrial fission and mitophagic proteins. Rehabilitative or pharmaceutical interventions to limit excess mitophagy may be effective therapies to protect paralyzed muscle mass and function. Muscle Nerve 58: 592–599, 2018</description><subject>Animals</subject><subject>Autophagy-Related Protein-1 Homolog - metabolism</subject><subject>Beclin-1 - metabolism</subject><subject>denervation</subject><subject>Fission</subject><subject>fusion</subject><subject>Fusion protein</subject><subject>Male</subject><subject>Markers</subject><subject>Membrane Proteins - metabolism</subject><subject>Mice</subject><subject>Microtubule-Associated Proteins - metabolism</subject><subject>Mitochondria</subject><subject>Mitochondrial Dynamics</subject><subject>Mitochondrial Proteins - metabolism</subject><subject>Mitophagy</subject><subject>Muscle Denervation</subject><subject>Muscle, Skeletal - innervation</subject><subject>Muscle, Skeletal - metabolism</subject><subject>Muscle, Skeletal - pathology</subject><subject>Muscles</subject><subject>Organ Size</subject><subject>Paralysis</subject><subject>Peripheral Nerve Injuries - metabolism</subject><subject>Phosphoproteins</subject><subject>Protein Kinases - metabolism</subject><subject>Proteins</subject><subject>PTEN-induced putative kinase</subject><subject>Rodents</subject><subject>Sciatic nerve</subject><subject>Sciatic Nerve - injuries</subject><subject>Skeletal muscle</subject><subject>Surgery</subject><subject>Unloading</subject><subject>Western blotting</subject><issn>0148-639X</issn><issn>1097-4598</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><recordid>eNp1kc9O3DAQhy0EgoVy4AWQJS5FahY7TmL7iBD_JKoeAKm3yOuMWaPEXuyEwkv0mXHIwgGJ0xzm-30zo0HogJI5JSQ_6YY4zysq-QaaUSJ5VpRSbKIZoYXIKib_7qDdGB8JIVRUfBvtsJQSZS5m6P9p20NQvfUuYutwZ3uvl941waoWGxtj6vzCZpiqcs07slqqB6vxKvgeUgpeVgHe0dHRLwE_qNgHrx10dojYm5TSgJVJw7DCUds0UmMH4RlwH5SLoMcdfqAto9oI--u6h-4vzu_OrrKbP5fXZ6c3mS7SmZmggldUGGIMY9xQXRpDlGx01QghuFwsREFYziQoBmVBCqoXwCSRhcmBM8n20M_Jmy54GiD2dWejhrZVDvwQ65xwxnJeyRE9-oI--iG4tF2dU1qVgjExUscTpYOPMYCpV8F2KrzWlNTjk-pu1I5PSuzh2jgsOmg-yY-vJOBkAv7ZFl6_N9W_728n5RuCoZ3O</recordid><startdate>201810</startdate><enddate>201810</enddate><creator>Graham, Zachary A.</creator><creator>Harlow, Lauren</creator><creator>Bauman, William A.</creator><creator>Cardozo, Christopher P.</creator><general>Wiley Subscription Services, Inc</general><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>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TS</scope><scope>7U7</scope><scope>7U9</scope><scope>C1K</scope><scope>H94</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope></search><sort><creationdate>201810</creationdate><title>Alterations in mitochondrial fission, fusion, and mitophagic protein expression in the gastrocnemius of mice after a sciatic nerve transection</title><author>Graham, Zachary A. ; Harlow, Lauren ; Bauman, William A. ; Cardozo, Christopher P.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4197-8187618f0ff337f1c5ff0a9dc6d88879bb8403239ea3e54041cbe39094f2e7393</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Animals</topic><topic>Autophagy-Related Protein-1 Homolog - metabolism</topic><topic>Beclin-1 - metabolism</topic><topic>denervation</topic><topic>Fission</topic><topic>fusion</topic><topic>Fusion protein</topic><topic>Male</topic><topic>Markers</topic><topic>Membrane Proteins - metabolism</topic><topic>Mice</topic><topic>Microtubule-Associated Proteins - metabolism</topic><topic>Mitochondria</topic><topic>Mitochondrial Dynamics</topic><topic>Mitochondrial Proteins - metabolism</topic><topic>Mitophagy</topic><topic>Muscle Denervation</topic><topic>Muscle, Skeletal - innervation</topic><topic>Muscle, Skeletal - metabolism</topic><topic>Muscle, Skeletal - pathology</topic><topic>Muscles</topic><topic>Organ Size</topic><topic>Paralysis</topic><topic>Peripheral Nerve Injuries - metabolism</topic><topic>Phosphoproteins</topic><topic>Protein Kinases - metabolism</topic><topic>Proteins</topic><topic>PTEN-induced putative kinase</topic><topic>Rodents</topic><topic>Sciatic nerve</topic><topic>Sciatic Nerve - injuries</topic><topic>Skeletal muscle</topic><topic>Surgery</topic><topic>Unloading</topic><topic>Western blotting</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Graham, Zachary A.</creatorcontrib><creatorcontrib>Harlow, Lauren</creatorcontrib><creatorcontrib>Bauman, William A.</creatorcontrib><creatorcontrib>Cardozo, Christopher P.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Physical Education Index</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><jtitle>Muscle & nerve</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Graham, Zachary A.</au><au>Harlow, Lauren</au><au>Bauman, William A.</au><au>Cardozo, Christopher P.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Alterations in mitochondrial fission, fusion, and mitophagic protein expression in the gastrocnemius of mice after a sciatic nerve transection</atitle><jtitle>Muscle & nerve</jtitle><addtitle>Muscle Nerve</addtitle><date>2018-10</date><risdate>2018</risdate><volume>58</volume><issue>4</issue><spage>592</spage><epage>599</epage><pages>592-599</pages><issn>0148-639X</issn><eissn>1097-4598</eissn><abstract>ABSTRACT
Introduction
Paralysis and unloading of skeletal muscle leads to a rapid loss in muscle size, function and oxidative capacity. The reduction in metabolic capability after disuse leads to dysregulation and increased breakdown of mitochondria by mitophagy.
Methods
Eight‐week‐old C57BL/6 male mice were given a sham surgery or sciatic nerve transection. Animals were euthanized at 7, 14, 21, or 35 days postsurgery. Whole gastrocnemius muscles were isolated from the animal, weighed and used for Western blotting.
Results
Markers of mitochondrial fusion were reduced while fission proteins were elevated following a sciatic nerve transection. There were elevations in phosphorylated unc‐51‐like kinase 1 (ULK1S555) and total expression of Beclin1, and of the mitophagy markers PINK1, p62, and microtubule‐associated proteins 1A/1B light chain 3b (LC3‐II).
Conclusions
Paralysis of the gastrocnemius leads to a progressive elevation in expression of mitochondrial fission and mitophagic proteins. Rehabilitative or pharmaceutical interventions to limit excess mitophagy may be effective therapies to protect paralyzed muscle mass and function. Muscle Nerve 58: 592–599, 2018</abstract><cop>United States</cop><pub>Wiley Subscription Services, Inc</pub><pmid>30028528</pmid><doi>10.1002/mus.26197</doi><tpages>8</tpages></addata></record> |
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| subjects | Animals Autophagy-Related Protein-1 Homolog - metabolism Beclin-1 - metabolism denervation Fission fusion Fusion protein Male Markers Membrane Proteins - metabolism Mice Microtubule-Associated Proteins - metabolism Mitochondria Mitochondrial Dynamics Mitochondrial Proteins - metabolism Mitophagy Muscle Denervation Muscle, Skeletal - innervation Muscle, Skeletal - metabolism Muscle, Skeletal - pathology Muscles Organ Size Paralysis Peripheral Nerve Injuries - metabolism Phosphoproteins Protein Kinases - metabolism Proteins PTEN-induced putative kinase Rodents Sciatic nerve Sciatic Nerve - injuries Skeletal muscle Surgery Unloading Western blotting |
| title | Alterations in mitochondrial fission, fusion, and mitophagic protein expression in the gastrocnemius of mice after a sciatic nerve transection |
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