The influence of passive stretch and NF-kappaB inhibitors on the morphology of dystrophic muscle fibers

Ashley Siegel, S Henley, A Zimmerman, M Miles, R Plummer, J Kurz, F Balch, J A Rhodes, G L Shinn, C G Carlson

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6 Citations (Scopus)

Abstract

The triangularis sterni (TS) is an expiratory muscle that is passively stretched during inspiration. The magnitude of passive stretch depends upon the location of individual fibers within the TS muscle, with fibers located more caudally being stretched approximately 5 to 10 more than fibers in the cephalad region. In the mdx mouse model for muscular dystrophy, the TS exhibits severe pathological alterations that are ameliorated by treatment with inhibitors of the NF-kappaB pathway. The purpose of this study was to assess the influence of passive stretch in vivo on fiber morphology in nondystrophic and mdx TS muscles, and the morphological benefits of treating mdx mice with two distinct NF-kappaB inhibitors, pyrrolidine dithiocarbamate (PDTC), and ursodeoxycholic acid (UDCA). Transmission electron microscopy revealed Z-line streaming, hypercontraction, and disassociation of the plasma membrane from the basal lamina in mdx fibers. In both nondystrophic and mdx TS muscles, fiber density was larger in more caudal regions. In comparison with nondystrophic TS, fibers in the mdx TS exhibited substantial reductions in diameter throughout all regions. In vivo treatment with either PDTC or UDCA tended to increase fiber diameter in the middle and decrease fiber diameter in the caudal TS, while reducing centronucleation in the middle region. These results suggest that passive stretch induces hypercontraction and plasma membrane abnormalities in dystrophic muscle, and that differences in the magnitude of passive stretch may influence fiber morphology and the actions of NF-kappaB inhibitors on dystrophic morphology.
Original languageEnglish
Pages (from-to)132 - 144
Number of pages13
JournalAnatomical Record
Volume294
Issue number1
DOIs
Publication statusPublished - 2011
Externally publishedYes

Cite this

Siegel, A., Henley, S., Zimmerman, A., Miles, M., Plummer, R., Kurz, J., ... Carlson, C. G. (2011). The influence of passive stretch and NF-kappaB inhibitors on the morphology of dystrophic muscle fibers. Anatomical Record, 294(1), 132 - 144. https://doi.org/10.1002/ar.21294
Siegel, Ashley ; Henley, S ; Zimmerman, A ; Miles, M ; Plummer, R ; Kurz, J ; Balch, F ; Rhodes, J A ; Shinn, G L ; Carlson, C G. / The influence of passive stretch and NF-kappaB inhibitors on the morphology of dystrophic muscle fibers. In: Anatomical Record. 2011 ; Vol. 294, No. 1. pp. 132 - 144.
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abstract = "The triangularis sterni (TS) is an expiratory muscle that is passively stretched during inspiration. The magnitude of passive stretch depends upon the location of individual fibers within the TS muscle, with fibers located more caudally being stretched approximately 5 to 10 more than fibers in the cephalad region. In the mdx mouse model for muscular dystrophy, the TS exhibits severe pathological alterations that are ameliorated by treatment with inhibitors of the NF-kappaB pathway. The purpose of this study was to assess the influence of passive stretch in vivo on fiber morphology in nondystrophic and mdx TS muscles, and the morphological benefits of treating mdx mice with two distinct NF-kappaB inhibitors, pyrrolidine dithiocarbamate (PDTC), and ursodeoxycholic acid (UDCA). Transmission electron microscopy revealed Z-line streaming, hypercontraction, and disassociation of the plasma membrane from the basal lamina in mdx fibers. In both nondystrophic and mdx TS muscles, fiber density was larger in more caudal regions. In comparison with nondystrophic TS, fibers in the mdx TS exhibited substantial reductions in diameter throughout all regions. In vivo treatment with either PDTC or UDCA tended to increase fiber diameter in the middle and decrease fiber diameter in the caudal TS, while reducing centronucleation in the middle region. These results suggest that passive stretch induces hypercontraction and plasma membrane abnormalities in dystrophic muscle, and that differences in the magnitude of passive stretch may influence fiber morphology and the actions of NF-kappaB inhibitors on dystrophic morphology.",
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Siegel, A, Henley, S, Zimmerman, A, Miles, M, Plummer, R, Kurz, J, Balch, F, Rhodes, JA, Shinn, GL & Carlson, CG 2011, 'The influence of passive stretch and NF-kappaB inhibitors on the morphology of dystrophic muscle fibers', Anatomical Record, vol. 294, no. 1, pp. 132 - 144. https://doi.org/10.1002/ar.21294

The influence of passive stretch and NF-kappaB inhibitors on the morphology of dystrophic muscle fibers. / Siegel, Ashley; Henley, S; Zimmerman, A; Miles, M; Plummer, R; Kurz, J; Balch, F; Rhodes, J A; Shinn, G L; Carlson, C G.

In: Anatomical Record, Vol. 294, No. 1, 2011, p. 132 - 144.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - The influence of passive stretch and NF-kappaB inhibitors on the morphology of dystrophic muscle fibers

AU - Siegel, Ashley

AU - Henley, S

AU - Zimmerman, A

AU - Miles, M

AU - Plummer, R

AU - Kurz, J

AU - Balch, F

AU - Rhodes, J A

AU - Shinn, G L

AU - Carlson, C G

PY - 2011

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N2 - The triangularis sterni (TS) is an expiratory muscle that is passively stretched during inspiration. The magnitude of passive stretch depends upon the location of individual fibers within the TS muscle, with fibers located more caudally being stretched approximately 5 to 10 more than fibers in the cephalad region. In the mdx mouse model for muscular dystrophy, the TS exhibits severe pathological alterations that are ameliorated by treatment with inhibitors of the NF-kappaB pathway. The purpose of this study was to assess the influence of passive stretch in vivo on fiber morphology in nondystrophic and mdx TS muscles, and the morphological benefits of treating mdx mice with two distinct NF-kappaB inhibitors, pyrrolidine dithiocarbamate (PDTC), and ursodeoxycholic acid (UDCA). Transmission electron microscopy revealed Z-line streaming, hypercontraction, and disassociation of the plasma membrane from the basal lamina in mdx fibers. In both nondystrophic and mdx TS muscles, fiber density was larger in more caudal regions. In comparison with nondystrophic TS, fibers in the mdx TS exhibited substantial reductions in diameter throughout all regions. In vivo treatment with either PDTC or UDCA tended to increase fiber diameter in the middle and decrease fiber diameter in the caudal TS, while reducing centronucleation in the middle region. These results suggest that passive stretch induces hypercontraction and plasma membrane abnormalities in dystrophic muscle, and that differences in the magnitude of passive stretch may influence fiber morphology and the actions of NF-kappaB inhibitors on dystrophic morphology.

AB - The triangularis sterni (TS) is an expiratory muscle that is passively stretched during inspiration. The magnitude of passive stretch depends upon the location of individual fibers within the TS muscle, with fibers located more caudally being stretched approximately 5 to 10 more than fibers in the cephalad region. In the mdx mouse model for muscular dystrophy, the TS exhibits severe pathological alterations that are ameliorated by treatment with inhibitors of the NF-kappaB pathway. The purpose of this study was to assess the influence of passive stretch in vivo on fiber morphology in nondystrophic and mdx TS muscles, and the morphological benefits of treating mdx mice with two distinct NF-kappaB inhibitors, pyrrolidine dithiocarbamate (PDTC), and ursodeoxycholic acid (UDCA). Transmission electron microscopy revealed Z-line streaming, hypercontraction, and disassociation of the plasma membrane from the basal lamina in mdx fibers. In both nondystrophic and mdx TS muscles, fiber density was larger in more caudal regions. In comparison with nondystrophic TS, fibers in the mdx TS exhibited substantial reductions in diameter throughout all regions. In vivo treatment with either PDTC or UDCA tended to increase fiber diameter in the middle and decrease fiber diameter in the caudal TS, while reducing centronucleation in the middle region. These results suggest that passive stretch induces hypercontraction and plasma membrane abnormalities in dystrophic muscle, and that differences in the magnitude of passive stretch may influence fiber morphology and the actions of NF-kappaB inhibitors on dystrophic morphology.

UR - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=21157924

U2 - 10.1002/ar.21294

DO - 10.1002/ar.21294

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JO - Anatomical Record

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SN - 1932-8486

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