{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T19:46:11Z","timestamp":1788291971793,"version":"build-2803163510"},"reference-count":96,"publisher":"Wiley","issue":"23","license":[{"start":{"date-parts":[[2023,10,21]],"date-time":"2023-10-21T00:00:00Z","timestamp":1697846400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2023,12]]},"abstract":"<jats:sec><jats:title>Abstract<\/jats:title><jats:p>Duchenne muscular dystrophy (DMD) is a fatal X\u2010linked disease characterised by severe muscle wasting. The mechanisms underlying the DMD pathology likely involve the interaction between inflammation, oxidative stress and impaired Ca<jats:sup>2+<\/jats:sup> signalling. Hypochlorous acid (HOCl) is a highly reactive oxidant produced endogenously via myeloperoxidase; an enzyme secreted by neutrophils that is significantly elevated in dystrophic muscle. Oxidation of Ca<jats:sup>2+<\/jats:sup>\u2010handling proteins by HOCl may impair Ca<jats:sup>2+<\/jats:sup> signalling. This study aimed to determine the effects of HOCl on skeletal muscle function and its potential contribution to the dystrophic pathology. Extensor digitorum longus (EDL), soleus and interosseous muscles were surgically isolated from anaesthetised C57 (wild\u2010type) and mdx (dystrophic) mice for measurement of <jats:italic>ex vivo<\/jats:italic> force production and intracellular Ca<jats:sup>2+<\/jats:sup> concentration. In whole EDL muscle, HOCl (200\u00a0\u03bcM) significantly decreased maximal force and increased resting muscle tension which was only partially reversible by dithiothreitol. The effects of HOCl (200\u00a0\u03bcM) on maximal force in slow\u2010twitch soleus were lower than found in the fast\u2010twitch EDL muscle. In single interosseous myofibres, HOCl (10\u00a0\u03bcM) significantly increased resting intracellular Ca<jats:sup>2+<\/jats:sup> concentration and decreased Ca<jats:sup>2+<\/jats:sup> transient amplitude. These effects of HOCl were reduced by the application of tetracaine, Gd<jats:sup>3+<\/jats:sup> or streptomycin, implicating involvement of ryanodine receptors and transient receptor potential channels. These results demonstrate the potent effects of HOCl on skeletal muscle function potentially mediated by HOCl\u2010induced oxidation to Ca<jats:sup>2+<\/jats:sup> signalling proteins. Hence, HOCl may provide a link between chronic inflammation, oxidative stress and impaired Ca<jats:sup>2+<\/jats:sup> handling that is characteristic of DMD and presents a potential therapeutic target for DMD.\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp15781-gra-0001-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p><\/jats:sec><jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Duchenne muscular dystrophy is a fatal genetic disease with pathological mechanisms which involve the complex interaction of chronic inflammation, increased reactive oxygen species production and increased cytosolic Ca<jats:sup>2+<\/jats:sup> concentrations.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Hypochlorous acid can be endogenously produced by neutrophils via the enzyme myeloperoxidase. Both neutrophil and myeloperoxidase activity are increased in dystrophic mice.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>This study found that hypochlorous acid decreased muscle force production and increased cytosolic Ca<jats:sup>2+<\/jats:sup> concentrations in isolated muscles from wild\u2010type and dystrophic mice at relatively low concentrations of hypochlorous acid.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>These results indicate that hypochlorous acid may be key in the Duchenne muscular dystrophy disease pathology and may provide a unifying link between the chronic inflammation, increased reactive oxygen species production and increased cytosolic Ca<jats:sup>2+<\/jats:sup> concentrations observed in Duchenne muscular dystrophy.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Hypochlorous acid production may be a potential target for therapeutic treatments of Duchenne muscular dystrophy.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1113\/jp285263","type":"journal-article","created":{"date-parts":[[2023,10,21]],"date-time":"2023-10-21T08:14:38Z","timestamp":1697876078000},"page":"5257-5275","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Hypochlorous acid exposure impairs skeletal muscle function and Ca<sup>2+<\/sup> signalling: implications for Duchenne muscular dystrophy pathology"],"prefix":"10.1113","volume":"601","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6469-7922","authenticated-orcid":false,"given":"Thomas A.","family":"Lea","sequence":"first","affiliation":[{"name":"School of Human Sciences University of Western Australia  Perth Western Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter M.","family":"Panizza","sequence":"additional","affiliation":[{"name":"School of Human Sciences University of Western Australia  Perth Western Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1257-8200","authenticated-orcid":false,"given":"Peter G.","family":"Arthur","sequence":"additional","affiliation":[{"name":"School of Molecular Sciences University of Western Australia  Perth Western Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony J.","family":"Bakker","sequence":"additional","affiliation":[{"name":"School of Human Sciences University of Western Australia  Perth Western Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4400-0817","authenticated-orcid":false,"given":"Gavin J.","family":"Pinniger","sequence":"additional","affiliation":[{"name":"School of Human Sciences University of Western Australia  Perth Western Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,10,21]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacbts.2016.09.004"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1998.565bn.x"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.00-0507fje"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2021.112968"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2005.7.870"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4598(200001)23:1<106::AID-MUS14>3.0.CO;2-D"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2001.012872"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.016014"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.1916"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmor.1052210207"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1998.275.2.C619"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2016.02.016"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-510X(87)90219-X"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.snb.2022.132545"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0970-05.2005"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2006.04.014"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.12.6746"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-021-03191-9"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00712152"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.880070903"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20151227"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2002.020487"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)62270-5"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2006.09.016"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-002-0854-5"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.21121"},{"key":"e_1_2_5_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jocn.2022.10.017"},{"key":"e_1_2_5_29_1","doi-asserted-by":"publisher","DOI":"10.3109\/10715762.2011.590136"},{"key":"e_1_2_5_30_1","doi-asserted-by":"publisher","DOI":"10.1139\/y91-249"},{"issue":"4","key":"e_1_2_5_31_1","first-page":"H1321","article-title":"Dithiothreitol restores contractile function to oxidant\u2010injured cardiac muscle","volume":"4","author":"Eley D.","year":"1989","journal-title":"American Journal of Physiology"},{"key":"e_1_2_5_32_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.69.4.1132"},{"key":"e_1_2_5_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/0960-8966(91)90039-U"},{"key":"e_1_2_5_34_1","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1998.84.2.425"},{"key":"e_1_2_5_35_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00645.2002"},{"key":"e_1_2_5_36_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2001.013043"},{"key":"e_1_2_5_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/344670a0"},{"key":"e_1_2_5_38_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0001762"},{"key":"e_1_2_5_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.talanta.2020.122030"},{"key":"e_1_2_5_40_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.032003"},{"key":"e_1_2_5_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2018.06.252"},{"key":"e_1_2_5_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)83641-4"},{"issue":"2","key":"e_1_2_5_43_1","first-page":"231","article-title":"The pharmacology of mechanogated membrane ion channels","volume":"48","author":"Hamill O.","year":"1996","journal-title":"Pharmacological Reviews"},{"key":"e_1_2_5_44_1","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1996.80.2.670"},{"key":"e_1_2_5_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2006.06.011"},{"key":"e_1_2_5_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2013.09.024"},{"key":"e_1_2_5_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.acthis.2022.151959"},{"key":"e_1_2_5_48_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddn408"},{"key":"e_1_2_5_49_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awv184"},{"key":"e_1_2_5_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-77197-6"},{"key":"e_1_2_5_51_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.50978"},{"key":"e_1_2_5_52_1","doi-asserted-by":"publisher","DOI":"10.1139\/Y09-117"},{"key":"e_1_2_5_53_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10654-020-00613-8"},{"key":"e_1_2_5_54_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13395-020-0221-2"},{"key":"e_1_2_5_55_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00374578"},{"key":"e_1_2_5_56_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00341.2014"},{"key":"e_1_2_5_57_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddq339"},{"key":"e_1_2_5_58_1","first-page":"184","article-title":"Density and composition of mammalian muscle","volume":"9","author":"Mendez J.","year":"1960","journal-title":"Metabolism"},{"key":"e_1_2_5_59_1","doi-asserted-by":"publisher","DOI":"10.3390\/metabo12020193"},{"key":"e_1_2_5_60_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1736"},{"key":"e_1_2_5_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-510X(93)90027-V"},{"key":"e_1_2_5_62_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2012.243279"},{"key":"e_1_2_5_63_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2006.114090"},{"key":"e_1_2_5_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbapap.2011.08.005"},{"key":"e_1_2_5_65_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi801080x"},{"key":"e_1_2_5_66_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.111.031716"},{"key":"e_1_2_5_67_1","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.119.013501"},{"key":"e_1_2_5_68_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjp.2008.285"},{"key":"e_1_2_5_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2019.10.415"},{"key":"e_1_2_5_70_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2000.2.1-5"},{"key":"e_1_2_5_71_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI114472"},{"key":"e_1_2_5_72_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.109.206581"},{"key":"e_1_2_5_73_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0035712"},{"key":"e_1_2_5_74_1","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/181260"},{"key":"e_1_2_5_75_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2016.00632"},{"key":"e_1_2_5_76_1","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/8892312"},{"key":"e_1_2_5_77_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.18.10909"},{"key":"e_1_2_5_78_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12640-011-9294-3"},{"key":"e_1_2_5_79_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2014.04.024"},{"issue":"4","key":"e_1_2_5_80_1","first-page":"H1597","article-title":"Hypochlorous acid and chloramines increase endothelial permeability: Possible involvement of cellular zinc","volume":"264","author":"Tatsumi T.","year":"1994","journal-title":"American Journal of Physiology"},{"key":"e_1_2_5_81_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2013.07.009"},{"key":"e_1_2_5_82_1","doi-asserted-by":"publisher","DOI":"10.1371\/currents.md.77be6ec30e8caf19529a00417614a072"},{"key":"e_1_2_5_83_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP271418"},{"key":"e_1_2_5_84_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0187317"},{"key":"e_1_2_5_85_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2011.11.007"},{"key":"e_1_2_5_86_1","doi-asserted-by":"publisher","DOI":"10.1111\/febs.12142"},{"key":"e_1_2_5_87_1","doi-asserted-by":"publisher","DOI":"10.1039\/D0AN00642D"},{"key":"e_1_2_5_88_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1357-2725(99)00095-3"},{"issue":"6","key":"e_1_2_5_89_1","first-page":"707","article-title":"Damage and inflammation in muscular dystrophy: Potential implications and relationships with autoimmune myositis","volume":"17","author":"Tidball J.","year":"2005","journal-title":"Current Opinion in Pharmacology"},{"key":"e_1_2_5_90_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M202549200"},{"key":"e_1_2_5_91_1","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines9101366"},{"key":"e_1_2_5_92_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10974-019-09563-5"},{"key":"e_1_2_5_93_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(88)90463-1"},{"key":"e_1_2_5_94_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI110652"},{"key":"e_1_2_5_95_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0891-5849(99)00051-9"},{"key":"e_1_2_5_96_1","doi-asserted-by":"publisher","DOI":"10.31635\/ccschem.021.202101108"},{"key":"e_1_2_5_97_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2004.075275"}],"container-title":["The Journal of Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/JP285263","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,12,16]],"date-time":"2023-12-16T09:27:11Z","timestamp":1702718831000},"score":1,"resource":{"primary":{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/10.1113\/JP285263"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,21]]},"references-count":96,"journal-issue":{"issue":"23","published-print":{"date-parts":[[2023,12]]}},"alternative-id":["10.1113\/JP285263"],"URL":"https:\/\/doi.org\/10.1113\/jp285263","archive":["Portico"],"relation":{},"ISSN":["0022-3751","1469-7793"],"issn-type":[{"value":"0022-3751","type":"print"},{"value":"1469-7793","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,21]]},"assertion":[{"value":"2023-07-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-10-09","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-10-21","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}