Ligand-induced rapid skeletal muscle atrophy in HSA-Fv2E-PERK transgenic mice.
Formation of 43S and 48S preinitiation complexes plays an important role in muscle protein synthesis. There is no muscle-wasting mouse model caused by a repressed 43S preinitiation complex assembly.The aim of the present study was to develop a convenient mouse model of skeletal muscle wasting with r...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2017-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC5482508?pdf=render |
| _version_ | 1818215181458604032 |
|---|---|
| author | Masato Miyake Masashi Kuroda Hiroshi Kiyonari Kenji Takehana Satoshi Hisanaga Masatoshi Morimoto Jun Zhang Miho Oyadomari Hiroshi Sakaue Seiichi Oyadomari |
| author_facet | Masato Miyake Masashi Kuroda Hiroshi Kiyonari Kenji Takehana Satoshi Hisanaga Masatoshi Morimoto Jun Zhang Miho Oyadomari Hiroshi Sakaue Seiichi Oyadomari |
| author_sort | Masato Miyake |
| collection | DOAJ |
| description | Formation of 43S and 48S preinitiation complexes plays an important role in muscle protein synthesis. There is no muscle-wasting mouse model caused by a repressed 43S preinitiation complex assembly.The aim of the present study was to develop a convenient mouse model of skeletal muscle wasting with repressed 43S preinitiation complex assembly.A ligand-activatable PERK derivative Fv2E-PERK causes the phosphorylation of eukaryotic initiation factor 2α (eIF2α), which inhibits 43S preinitiation complex assembly. Thus, muscle atrophic phenotypes, intracellular signaling pathways, and intracellular free amino acid profiles were investigated in human skeletal muscle α-actin (HSA) promoter-driven Fv2E-PERK transgenic (Tg) mice.HSA-Fv2E-PERK Tg mice treated with the artificial dimerizer AP20187 phosphorylates eIF2α in skeletal muscles and leads to severe muscle atrophy within a few days of ligand injection. Muscle atrophy was accompanied by a counter regulatory activation of mTORC1 signaling. Moreover, intracellular free amino acid levels were distinctively altered in the skeletal muscles of HSA-Fv2E-PERK Tg mice.As a novel model of muscle wasting, HSA-Fv2E-PERK Tg mice provide a convenient tool for studying the pathogenesis of muscle loss and for assessing putative therapeutics. |
| first_indexed | 2024-12-12T06:32:00Z |
| format | Article |
| id | doaj.art-90cdcc369a424f47be5c274196d1a1ba |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-12T06:32:00Z |
| publishDate | 2017-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-90cdcc369a424f47be5c274196d1a1ba2022-12-22T00:34:33ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01126e017995510.1371/journal.pone.0179955Ligand-induced rapid skeletal muscle atrophy in HSA-Fv2E-PERK transgenic mice.Masato MiyakeMasashi KurodaHiroshi KiyonariKenji TakehanaSatoshi HisanagaMasatoshi MorimotoJun ZhangMiho OyadomariHiroshi SakaueSeiichi OyadomariFormation of 43S and 48S preinitiation complexes plays an important role in muscle protein synthesis. There is no muscle-wasting mouse model caused by a repressed 43S preinitiation complex assembly.The aim of the present study was to develop a convenient mouse model of skeletal muscle wasting with repressed 43S preinitiation complex assembly.A ligand-activatable PERK derivative Fv2E-PERK causes the phosphorylation of eukaryotic initiation factor 2α (eIF2α), which inhibits 43S preinitiation complex assembly. Thus, muscle atrophic phenotypes, intracellular signaling pathways, and intracellular free amino acid profiles were investigated in human skeletal muscle α-actin (HSA) promoter-driven Fv2E-PERK transgenic (Tg) mice.HSA-Fv2E-PERK Tg mice treated with the artificial dimerizer AP20187 phosphorylates eIF2α in skeletal muscles and leads to severe muscle atrophy within a few days of ligand injection. Muscle atrophy was accompanied by a counter regulatory activation of mTORC1 signaling. Moreover, intracellular free amino acid levels were distinctively altered in the skeletal muscles of HSA-Fv2E-PERK Tg mice.As a novel model of muscle wasting, HSA-Fv2E-PERK Tg mice provide a convenient tool for studying the pathogenesis of muscle loss and for assessing putative therapeutics.http://europepmc.org/articles/PMC5482508?pdf=render |
| spellingShingle | Masato Miyake Masashi Kuroda Hiroshi Kiyonari Kenji Takehana Satoshi Hisanaga Masatoshi Morimoto Jun Zhang Miho Oyadomari Hiroshi Sakaue Seiichi Oyadomari Ligand-induced rapid skeletal muscle atrophy in HSA-Fv2E-PERK transgenic mice. PLoS ONE |
| title | Ligand-induced rapid skeletal muscle atrophy in HSA-Fv2E-PERK transgenic mice. |
| title_full | Ligand-induced rapid skeletal muscle atrophy in HSA-Fv2E-PERK transgenic mice. |
| title_fullStr | Ligand-induced rapid skeletal muscle atrophy in HSA-Fv2E-PERK transgenic mice. |
| title_full_unstemmed | Ligand-induced rapid skeletal muscle atrophy in HSA-Fv2E-PERK transgenic mice. |
| title_short | Ligand-induced rapid skeletal muscle atrophy in HSA-Fv2E-PERK transgenic mice. |
| title_sort | ligand induced rapid skeletal muscle atrophy in hsa fv2e perk transgenic mice |
| url | http://europepmc.org/articles/PMC5482508?pdf=render |
| work_keys_str_mv | AT masatomiyake ligandinducedrapidskeletalmuscleatrophyinhsafv2eperktransgenicmice AT masashikuroda ligandinducedrapidskeletalmuscleatrophyinhsafv2eperktransgenicmice AT hiroshikiyonari ligandinducedrapidskeletalmuscleatrophyinhsafv2eperktransgenicmice AT kenjitakehana ligandinducedrapidskeletalmuscleatrophyinhsafv2eperktransgenicmice AT satoshihisanaga ligandinducedrapidskeletalmuscleatrophyinhsafv2eperktransgenicmice AT masatoshimorimoto ligandinducedrapidskeletalmuscleatrophyinhsafv2eperktransgenicmice AT junzhang ligandinducedrapidskeletalmuscleatrophyinhsafv2eperktransgenicmice AT mihooyadomari ligandinducedrapidskeletalmuscleatrophyinhsafv2eperktransgenicmice AT hiroshisakaue ligandinducedrapidskeletalmuscleatrophyinhsafv2eperktransgenicmice AT seiichioyadomari ligandinducedrapidskeletalmuscleatrophyinhsafv2eperktransgenicmice |