Endoplasmic reticulum stress in myotonic dystrophy type 1 muscle

Koji Ikezoe, Masayuki Nakamori, Hirokazu Furuya, Hajime Arahata, Soshi Kanemoto, Takashi Kimura, Kazunori Imaizumi, Masanori P. Takahashi, Saburo Sakoda, Naoki Fujii, Jun-Ichi Kira

Research output: Contribution to journalArticle

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Abstract

In myotonic dystrophy type 1 (DM1), alternative splicing of ryanodine receptor 1 (RyR1) and sarcoplasmic/endoplasmic reticulum Ca2+ ATPase (SERCA) genes has been reported. These proteins are essential for maintaining intracellular Ca2+ in skeletal muscle. To clarify involvement of endoplasmic reticulum (ER) stress in DM1 muscles, we examined the activation of ER stress-related proteins by immunohistochemistry, western blot analysis and RT-PCR. In four of five DM1 muscle biopsies, except for a muscle biopsy from a patient with the shortest CTG expansion and no myotonia, increased expression of GRP78 and calnexin, and phosphorylation of PERK and eIF-α were revealed in fibers with sarcoplasmic masses and in highly atrophic fibers with pyknotic nuclear clumps. Caspase-3 and -7 were also expressed in these fibers. Increased expression of GRP78 in these DM1 muscles was confirmed by western blot analysis. GRP78 mRNA and spliced isoform of XBP1 mRNA were also increased in DM1 muscle biopsies. Furthermore, we demonstrated increased expression of GRP78 in highly atrophic fibers with pyknotic nuclear clumps in all three muscle biopsies from neurogenic muscular atrophies. However, five muscle biopsies from central core disease presumably with disturbed intracellular Ca2+ homeostasis and a muscle biopsy from paramyotonia congenita with myotonia showed no activation of these proteins. Taken together, ER stress is involved in muscle wasting in DM1. However, it seems to be evoked not only by disrupted intracellular Ca2+ homeostasis.

Original languageEnglish
Pages (from-to)527-535
Number of pages9
JournalActa Neuropathologica
Volume114
Issue number5
DOIs
Publication statusPublished - Nov 1 2007

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Myotonic Dystrophy
Endoplasmic Reticulum Stress
Muscles
Biopsy
Myotonia
Central Core Myopathy
Homeostasis
Myotonic Disorders
Western Blotting
Calnexin
RNA Isoforms
Caspase 7
Ryanodine Receptor Calcium Release Channel
Muscular Atrophy
Calcium-Transporting ATPases
Alternative Splicing
Sarcoplasmic Reticulum
Heat-Shock Proteins
Caspase 3
Endoplasmic Reticulum

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

Cite this

Ikezoe, K., Nakamori, M., Furuya, H., Arahata, H., Kanemoto, S., Kimura, T., ... Kira, J-I. (2007). Endoplasmic reticulum stress in myotonic dystrophy type 1 muscle. Acta Neuropathologica, 114(5), 527-535. https://doi.org/10.1007/s00401-007-0267-9

Endoplasmic reticulum stress in myotonic dystrophy type 1 muscle. / Ikezoe, Koji; Nakamori, Masayuki; Furuya, Hirokazu; Arahata, Hajime; Kanemoto, Soshi; Kimura, Takashi; Imaizumi, Kazunori; Takahashi, Masanori P.; Sakoda, Saburo; Fujii, Naoki; Kira, Jun-Ichi.

In: Acta Neuropathologica, Vol. 114, No. 5, 01.11.2007, p. 527-535.

Research output: Contribution to journalArticle

Ikezoe, K, Nakamori, M, Furuya, H, Arahata, H, Kanemoto, S, Kimura, T, Imaizumi, K, Takahashi, MP, Sakoda, S, Fujii, N & Kira, J-I 2007, 'Endoplasmic reticulum stress in myotonic dystrophy type 1 muscle', Acta Neuropathologica, vol. 114, no. 5, pp. 527-535. https://doi.org/10.1007/s00401-007-0267-9
Ikezoe K, Nakamori M, Furuya H, Arahata H, Kanemoto S, Kimura T et al. Endoplasmic reticulum stress in myotonic dystrophy type 1 muscle. Acta Neuropathologica. 2007 Nov 1;114(5):527-535. https://doi.org/10.1007/s00401-007-0267-9
Ikezoe, Koji ; Nakamori, Masayuki ; Furuya, Hirokazu ; Arahata, Hajime ; Kanemoto, Soshi ; Kimura, Takashi ; Imaizumi, Kazunori ; Takahashi, Masanori P. ; Sakoda, Saburo ; Fujii, Naoki ; Kira, Jun-Ichi. / Endoplasmic reticulum stress in myotonic dystrophy type 1 muscle. In: Acta Neuropathologica. 2007 ; Vol. 114, No. 5. pp. 527-535.
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