Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

Antioxidants reduce muscular dystrophy in the dy2J/dy2J mouse model of laminin α2 chain-deficient muscular dystrophy

Harandi, Vahid M. LU ; Oliveira, Bernardo Moreira Soares LU orcid ; Allamand, Valérie LU ; Friberg, Ariana ; Fontes-Oliveira, Cibely C. LU and Durbeej, Madeleine LU (2020) In Antioxidants 9(3).
Abstract

Congenital muscular dystrophy with laminin α2 chain-deficiency (LAMA2-CMD) is a severe neuromuscular disorder without a cure. Using transcriptome and proteome profiling as well as functional assays, we previously demonstrated significant metabolic impairment in skeletal muscle from LAMA2-CMD patients and mouse models. Reactive oxygen species (ROS) increase when oxygen homeostasis is not maintained and, here, we investigate whether oxidative stress indeed is involved in the pathogenesis of LAMA2-CMD. We also analyze the effects of two antioxidant molecules, N-acetyl-L-cysteine (NAC) and vitamin E, on disease progression in the dy2J/dy2J mouse model of LAMA2-CMD. We demonstrate increased ROS levels in LAMA2-CMD mouse... (More)

Congenital muscular dystrophy with laminin α2 chain-deficiency (LAMA2-CMD) is a severe neuromuscular disorder without a cure. Using transcriptome and proteome profiling as well as functional assays, we previously demonstrated significant metabolic impairment in skeletal muscle from LAMA2-CMD patients and mouse models. Reactive oxygen species (ROS) increase when oxygen homeostasis is not maintained and, here, we investigate whether oxidative stress indeed is involved in the pathogenesis of LAMA2-CMD. We also analyze the effects of two antioxidant molecules, N-acetyl-L-cysteine (NAC) and vitamin E, on disease progression in the dy2J/dy2J mouse model of LAMA2-CMD. We demonstrate increased ROS levels in LAMA2-CMD mouse and patient skeletal muscle. Furthermore, NAC treatment (150 mg/kg IP for 6 days/week for 3 weeks) led to muscle force loss prevention, reduced central nucleation and decreased the occurrence of apoptosis, inflammation, fibrosis and oxidative stress in LAMA2-CMD muscle. In addition, vitamin E (40 mg/kg oral gavage for 6 days/week for 2 weeks) improved morphological features and reduced inflammation and ROS levels in dy2J/dy2J skeletal muscle. We suggest that NAC and to some extent vitamin E might be potential future supportive treatments for LAMA2-CMD as they improve numerous pathological hallmarks of LAMA2-CMD.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Congenital muscular dystrophy, Laminin, Reactive oxygen species, Therapy
in
Antioxidants
volume
9
issue
3
article number
244
publisher
MDPI AG
external identifiers
  • scopus:85081992467
  • pmid:32197453
ISSN
2076-3921
DOI
10.3390/antiox9030244
language
English
LU publication?
yes
id
fddf1b1f-3c04-42c4-9791-624e4ccddf6d
date added to LUP
2020-04-07 09:17:21
date last changed
2024-09-04 20:11:36
@article{fddf1b1f-3c04-42c4-9791-624e4ccddf6d,
  abstract     = {{<p>Congenital muscular dystrophy with laminin α2 chain-deficiency (LAMA2-CMD) is a severe neuromuscular disorder without a cure. Using transcriptome and proteome profiling as well as functional assays, we previously demonstrated significant metabolic impairment in skeletal muscle from LAMA2-CMD patients and mouse models. Reactive oxygen species (ROS) increase when oxygen homeostasis is not maintained and, here, we investigate whether oxidative stress indeed is involved in the pathogenesis of LAMA2-CMD. We also analyze the effects of two antioxidant molecules, N-acetyl-L-cysteine (NAC) and vitamin E, on disease progression in the dy<sup>2J</sup>/dy<sup>2J</sup> mouse model of LAMA2-CMD. We demonstrate increased ROS levels in LAMA2-CMD mouse and patient skeletal muscle. Furthermore, NAC treatment (150 mg/kg IP for 6 days/week for 3 weeks) led to muscle force loss prevention, reduced central nucleation and decreased the occurrence of apoptosis, inflammation, fibrosis and oxidative stress in LAMA2-CMD muscle. In addition, vitamin E (40 mg/kg oral gavage for 6 days/week for 2 weeks) improved morphological features and reduced inflammation and ROS levels in dy<sup>2J</sup>/dy<sup>2J</sup> skeletal muscle. We suggest that NAC and to some extent vitamin E might be potential future supportive treatments for LAMA2-CMD as they improve numerous pathological hallmarks of LAMA2-CMD.</p>}},
  author       = {{Harandi, Vahid M. and Oliveira, Bernardo Moreira Soares and Allamand, Valérie and Friberg, Ariana and Fontes-Oliveira, Cibely C. and Durbeej, Madeleine}},
  issn         = {{2076-3921}},
  keywords     = {{Congenital muscular dystrophy; Laminin; Reactive oxygen species; Therapy}},
  language     = {{eng}},
  number       = {{3}},
  publisher    = {{MDPI AG}},
  series       = {{Antioxidants}},
  title        = {{Antioxidants reduce muscular dystrophy in the dy<sup>2J</sup>/dy<sup>2J</sup> mouse model of laminin α2 chain-deficient muscular dystrophy}},
  url          = {{http://dx.doi.org/10.3390/antiox9030244}},
  doi          = {{10.3390/antiox9030244}},
  volume       = {{9}},
  year         = {{2020}},
}