432P Hydrogen sulfide attenuates skeletal muscle abnormalities in a murine model of Duchenne muscular dystrophy
Duchenne muscular dystrophy (DMD) is a severe and incurable X-linked genetic disorder caused by a mutation in the DMD gene, encoding muscle structural protein, dystrophin. Dystrophin deficiency affects skeletal and cardiac muscles leading to premature death in young adulthood. Recently, we have demo...
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Published in: | Neuromuscular disorders : NMD Vol. 43; p. 104441 |
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Main Authors: | , , , , , , |
Format: | Journal Article |
Language: | English |
Published: |
Elsevier B.V
01-10-2024
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Online Access: | Get full text |
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Summary: | Duchenne muscular dystrophy (DMD) is a severe and incurable X-linked genetic disorder caused by a mutation in the DMD gene, encoding muscle structural protein, dystrophin. Dystrophin deficiency affects skeletal and cardiac muscles leading to premature death in young adulthood. Recently, we have demonstrated decreased expression of enzymes that generate hydrogen sulfide (H2S) in dystrophic muscles. We have also shown that treatment with the fast-releasing H2S donor, sodium hydrosulfide (NaHS), exerts moderate protective effects in a mouse model of DMD. Administration of the slow-releasing H2S donor (GYY4137) to the dystrophin-deficient mdx mice improved motor functions and decreased the level of muscle damage markers such as lactate dehydrogenase (LDH), creatine kinase (CK), and osteopontin (OPN). Histological, gene, and protein analyses of the gastrocnemius muscle and diaphragm of mdx mice revealed reduced inflammation and fibrosis. Moreover, decreased necrosis with improved muscle regeneration and angiogenesis were observed. The upregulation of phosphorylated AMPKα and cytoprotective heme oxygenase-1 (HO-1) with the anti-apoptotic effect through reducing caspase-3 and increasing AKT phosphorylation were also evident after the slow releaser of H2S. Overall, the administration of GYY4137 can ameliorate DMD progression in the skeletal muscles of mdx animals. More studies on other DMD-related pathologies, especially cardiomyopathies are warranted. |
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ISSN: | 0960-8966 |
DOI: | 10.1016/j.nmd.2024.07.312 |