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DOI	10.1073/pnas.2018342118
	Mitochondrial hydrogen sulfide supplementation improves health in the C. elegans Duchenne muscular dystrophy model
	Ellwood R.A.; Hewitt J.E.; Torregrossa R.; Philp A.M.; Hardee J.P.; Hughes S.; van de Klashorst D.; Gharahdaghi N.; Anupom T.; Slade L.; Deane C.S.; Cooke M.; Etheridge T.; Piasecki M.; Antebi A.; Lynch G.S.; Philp A.; Vanapalli S.A.; Whiteman M.; Szewczyk N.J.
发表日期	2021
ISSN	00278424
卷号	118 期号:9
英文摘要	Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder characterized by progressive muscle degeneration and weakness due to mutations in the dystrophin gene. The symptoms of DMD share similarities with those of accelerated aging. Recently, hydrogen sulfide (H2S) supplementation has been suggested to modulate the effects of age-related decline in muscle function, and metabolic H2S deficiencies have been implicated in affecting muscle mass in conditions such as phenylketonuria. We therefore evaluated the use of sodium GYY4137 (NaGYY), a H2S-releasing molecule, as a possible approach for DMD treatment. Using the dys-1(eg33) Caenorhabditis elegans DMD model, we found that NaGYY treatment (100 μM) improved movement, strength, gait, and muscle mitochondrial structure, similar to the gold-standard therapeutic treatment, prednisone (370 μM). The health improvements of either treatment required the action of the kinase JNK-1, the transcription factor SKN-1, and the NAD-dependent deacetylase SIR-2.1. The transcription factor DAF-16 was required for the health benefits of NaGYY treatment, but not prednisone treatment. AP39 (100 pM), a mitochondria-targeted H2S compound, also improved movement and strength in the dys-1(eg33) model, further implying that these improvements are mitochondria-based. Additionally, we found a decline in total sulfide and H2S-producing enzymes in dystrophin/utrophin knockout mice. Overall, our results suggest that H2S deficit may contribute to DMD pathology, and rectifying/overcoming the deficit with H2S delivery compounds has potential as a therapeutic approach to DMD treatment. © This open access article is distributed under Creative Commons Attribution License 4.0 (CC BY).
英文关键词	C. Elegans; Hydrogen sulfide; Mitochondria; Mouse; Muscle
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180499
作者单位	Medical Research Council (MRC), Versus Arthritis Centre for Musculoskeletal Ageing Research, Royal Derby Hospital, University of Nottingham, Derby, DE22 3DT, United Kingdom; Musculoskeletal Conditions, National Institute for Health Research, Nottingham Biomedical Research Centre, Derby, DE22 3DT, United Kingdom; Department of Chemical Engineering, Texas Tech University, Lubbock, TX 79409, United States; Molecular Genetics of Ageing, Max Planck Institute for Biology of Ageing, Cologne, 50931, Germany; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, 50931, Germany; University of Exeter Medical School, University of Exeter, Exeter, EX1 2LU, United Kingdom; Mitochondrial Metabolism and Ageing, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia; St. Vincent's Clinical School, University of New South Wales (UNSW) Medicine, University of New South Wales Sydney, Sydney, NSW 2052, Australia; Centre for Muscle Research, ...
推荐引用方式 GB/T 7714	Ellwood R.A.,Hewitt J.E.,Torregrossa R.,et al. Mitochondrial hydrogen sulfide supplementation improves health in the C. elegans Duchenne muscular dystrophy model[J],2021,118(9).
APA	Ellwood R.A..,Hewitt J.E..,Torregrossa R..,Philp A.M..,Hardee J.P..,...&Szewczyk N.J..(2021).Mitochondrial hydrogen sulfide supplementation improves health in the C. elegans Duchenne muscular dystrophy model.Proceedings of the National Academy of Sciences of the United States of America,118(9).
MLA	Ellwood R.A.,et al."Mitochondrial hydrogen sulfide supplementation improves health in the C. elegans Duchenne muscular dystrophy model".Proceedings of the National Academy of Sciences of the United States of America 118.9(2021).