{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,3]],"date-time":"2025-07-03T04:11:39Z","timestamp":1751515899538,"version":"3.41.0"},"reference-count":50,"publisher":"Canadian Science Publishing","issue":"11","license":[{"start":{"date-parts":[[2019,11,1]],"date-time":"2019-11-01T00:00:00Z","timestamp":1572566400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.nrcresearchpress.com\/page\/about\/CorporateTextAndDataMining"}],"content-domain":{"domain":["cdnsciencepub.com"],"crossmark-restriction":false},"short-container-title":["Can. J. Physiol. Pharmacol."],"published-print":{"date-parts":[[2019,11]]},"abstract":"<jats:p> Homocysteine, a non-proteinogenic amino acid but an important metabolic intermediate is generated as an integral component for the \u201c1-carbon metabolism\u201d during normal physiology. It is catabolized to cysteine via the transulfuration pathway resulting in the generation of hydrogen sulfide, a naturally endogenous byproduct. Genetics or metabolic derangement can alter homocysteine concentration leading to hyperhomocysteinemia (HHcy), a physiologically unfavorable condition that causes serious medical conditions including muscle wasting. HHcy environment can derail physiological processes by targeting biomolecules such as Akt; however, not much is known regarding the effects of HHcy on regulation of transcription factors such as forkhead box O (FOXO) proteins. Recently, hydrogen sulfide has been shown to be highly effective in alleviating the effects of HHcy by serving as an antiapoptotic factor, but role of FOXO and its interaction with hydrogen sulfide are yet to be established. In this review, we discuss role(s) of HHcy in skeletal muscle atrophy and how HHcy interact with FOXO and peroxisome proliferator-activated receptor gamma coactivator 1-alpha expressions that are relevant in musculoskeletal atrophy. Further, therapeutic intervention with hydrogen sulfide for harnessing its beneficial effects might help mitigate the dysregulated 1-carbon metabolism that happens to be the hallmark of HHcy-induced pathologies such as muscle atrophy. <\/jats:p>","DOI":"10.1139\/cjpp-2019-0227","type":"journal-article","created":{"date-parts":[[2019,7,3]],"date-time":"2019-07-03T21:37:35Z","timestamp":1562189855000},"page":"1013-1017","update-policy":"https:\/\/doi.org\/10.1139\/csp-crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Dysregulation of 1-carbon metabolism and muscle atrophy: potential roles of forkhead box O proteins and PPAR\u03b3 co-activator-1\u03b1"],"prefix":"10.1139","volume":"97","author":[{"given":"Anwesha","family":"Laha","sequence":"first","affiliation":[{"name":"Department of Physiology, University of Louisville School of Medicine, Louisville 40202, Kentucky, USA."},{"name":"Department of Physiology, University of Louisville School of Medicine, Louisville 40202, Kentucky, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mahavir","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of Louisville School of Medicine, Louisville 40202, Kentucky, USA."},{"name":"Department of Physiology, University of Louisville School of Medicine, Louisville 40202, Kentucky, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akash K.","family":"George","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of Louisville School of Medicine, Louisville 40202, Kentucky, USA."},{"name":"Department of Physiology, University of Louisville School of Medicine, Louisville 40202, Kentucky, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rubens P.","family":"Homme","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of Louisville School of Medicine, Louisville 40202, Kentucky, USA."},{"name":"Department of Physiology, University of Louisville School of Medicine, Louisville 40202, Kentucky, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suresh C.","family":"Tyagi","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of Louisville School of Medicine, Louisville 40202, Kentucky, USA."},{"name":"Department of Physiology, University of Louisville School of Medicine, Louisville 40202, Kentucky, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"155","reference":[{"doi-asserted-by":"publisher","key":"refg1\/ref1","DOI":"10.1523\/JNEUROSCI.16-03-01066.1996"},{"doi-asserted-by":"publisher","key":"refg2\/ref2","DOI":"10.3988\/jcn.2014.10.4.281"},{"doi-asserted-by":"publisher","key":"refg3\/ref3","DOI":"10.1073\/pnas.0405454101"},{"doi-asserted-by":"publisher","key":"refg4\/ref4","DOI":"10.1126\/science.1065874"},{"doi-asserted-by":"publisher","key":"refg5\/ref5","DOI":"10.1139\/H09-008"},{"doi-asserted-by":"publisher","key":"refg7\/ref7","DOI":"10.3389\/fphys.2014.00099"},{"doi-asserted-by":"publisher","key":"refg8\/ref8","DOI":"10.1128\/MCB.21.10.3534-3546.2001"},{"doi-asserted-by":"publisher","key":"refg9\/ref9","DOI":"10.1016\/S0092-8674(00)80595-4"},{"doi-asserted-by":"publisher","key":"refg10\/ref10","DOI":"10.1016\/j.cardiores.2007.05.026"},{"doi-asserted-by":"publisher","key":"refg11\/ref11","DOI":"10.1016\/j.cub.2007.01.008"},{"doi-asserted-by":"publisher","key":"refg12\/ref12","DOI":"10.1042\/BSR20130031"},{"doi-asserted-by":"publisher","key":"refg14\/ref14","DOI":"10.1155\/2010\/409168"},{"doi-asserted-by":"crossref","unstructured":"Damjanov, I. 2009. Chapter 21 - skeletal muscles. In Pathology Secrets (3rd ed.). Philadelphia, Mosby Pages. pp. 434\u2013447.","key":"refg15\/ref15","DOI":"10.1016\/B978-0-323-05594-9.00021-0"},{"doi-asserted-by":"publisher","key":"refg18\/ref18","DOI":"10.1289\/ehp.10531"},{"doi-asserted-by":"crossref","unstructured":"Gonin, J.M., and Wilcox, C.S. 2008. Chapter 64 - Hyperhomocysteinemia. In Therapy in Nephrology & Hypertension (3rd edition). Edited by C.S. Wilcox and W.B. Saunders. Philadelphia. pp. 725\u2013730.","key":"refg19\/ref19","DOI":"10.1016\/B978-141605484-9.50066-6"},{"doi-asserted-by":"publisher","key":"refg20\/ref20","DOI":"10.1016\/j.bbamcr.2011.01.007"},{"doi-asserted-by":"publisher","key":"refg21\/ref21","DOI":"10.1152\/ajpcell.00579.2003"},{"doi-asserted-by":"publisher","key":"refg22\/ref22","DOI":"10.1097\/SHK.0000000000000894"},{"doi-asserted-by":"publisher","key":"refg23\/ref23","DOI":"10.1111\/j.1749-6632.2012.06738.x"},{"doi-asserted-by":"publisher","key":"refg24\/ref24","DOI":"10.1007\/s11936-002-0016-2"},{"doi-asserted-by":"publisher","key":"refg25\/ref25","DOI":"10.1385\/MN:26:1:013"},{"doi-asserted-by":"publisher","key":"refg26\/ref26","DOI":"10.1016\/j.cmet.2011.03.020"},{"doi-asserted-by":"publisher","key":"refg27\/ref27","DOI":"10.1139\/cjpp-2018-0037"},{"doi-asserted-by":"publisher","key":"refg28\/ref28","DOI":"10.3389\/fphys.2018.01220"},{"doi-asserted-by":"publisher","key":"refg29\/ref29","DOI":"10.1073\/pnas.0709010104"},{"doi-asserted-by":"publisher","unstructured":"Leonardini, A., Laviola, L., Perrini, S., Natalicchio, A., and Giorgino, F. 2009. Cross-Talk between PPAR\u03b3 and insulin signaling and modulation of insulin sensitivity. 2009: 818945. 10.1155\/2009\/818945. PMID:20182551.","key":"refg30\/ref30","DOI":"10.1155\/2009\/818945. PMID:"},{"doi-asserted-by":"publisher","key":"refg31\/ref31","DOI":"10.1152\/ajpendo.90719.2008"},{"doi-asserted-by":"publisher","key":"refg32\/ref32","DOI":"10.1152\/advan.00052.2006"},{"doi-asserted-by":"publisher","key":"refg33\/ref33","DOI":"10.1016\/j.ymthe.2017.12.014"},{"doi-asserted-by":"publisher","key":"refg34\/ref34","DOI":"10.1152\/ajpcell.00147.2018"},{"doi-asserted-by":"publisher","key":"refg35\/ref35","DOI":"10.1139\/cjpp-2018-0501"},{"doi-asserted-by":"publisher","key":"refg36\/ref36","DOI":"10.1146\/annurev.med.60.041807.123308"},{"doi-asserted-by":"publisher","key":"refg37\/ref37","DOI":"10.1073\/pnas.1934283100"},{"doi-asserted-by":"publisher","key":"refg38\/ref38","DOI":"10.1016\/j.jacc.2007.05.017"},{"doi-asserted-by":"publisher","key":"refg39\/ref39","DOI":"10.1152\/ajpheart.00682.2009"},{"doi-asserted-by":"publisher","key":"refg40\/ref40","DOI":"10.1016\/S0165-6147(00)01559-5"},{"doi-asserted-by":"publisher","key":"refg41\/ref41","DOI":"10.1038\/s41598-017-03776-9"},{"doi-asserted-by":"publisher","key":"refg13\/ref13","DOI":"10.17226\/12741"},{"doi-asserted-by":"publisher","key":"refg42\/ref42","DOI":"10.1016\/j.febslet.2006.04.088"},{"doi-asserted-by":"publisher","key":"refg43\/ref43","DOI":"10.1016\/j.tcm.2012.07.003"},{"doi-asserted-by":"publisher","key":"refg44\/ref44","DOI":"10.1007\/s00018-013-1513-z"},{"doi-asserted-by":"publisher","key":"refg45\/ref45","DOI":"10.1016\/S0092-8674(04)00400-3"},{"doi-asserted-by":"publisher","key":"refg46\/ref46","DOI":"10.1073\/pnas.0607795103"},{"doi-asserted-by":"publisher","key":"refg47\/ref47","DOI":"10.1007\/s12013-010-9079-y"},{"doi-asserted-by":"publisher","key":"refg48\/ref48","DOI":"10.1038\/ncb1469"},{"doi-asserted-by":"publisher","key":"refg49\/ref49","DOI":"10.3390\/ijms140715074"},{"doi-asserted-by":"publisher","key":"refg50\/ref50","DOI":"10.3390\/ijms16011252"},{"doi-asserted-by":"publisher","key":"refg51\/ref51","DOI":"10.1016\/j.bbadis.2015.01.008"},{"doi-asserted-by":"publisher","key":"refg52\/ref52","DOI":"10.1155\/2014\/925350"},{"doi-asserted-by":"publisher","key":"refg53\/ref53","DOI":"10.1126\/science.1162667"}],"container-title":["Canadian Journal of Physiology and Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/cdnsciencepub.com\/doi\/full-xml\/10.1139\/cjpp-2019-0227","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/cdnsciencepub.com\/doi\/pdf\/10.1139\/cjpp-2019-0227","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T16:20:34Z","timestamp":1751473234000},"score":1,"resource":{"primary":{"URL":"https:\/\/cdnsciencepub.com\/doi\/10.1139\/cjpp-2019-0227"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,11]]},"references-count":50,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2019,11]]}},"alternative-id":["10.1139\/cjpp-2019-0227"],"URL":"https:\/\/doi.org\/10.1139\/cjpp-2019-0227","relation":{},"ISSN":["0008-4212","1205-7541"],"issn-type":[{"type":"print","value":"0008-4212"},{"type":"electronic","value":"1205-7541"}],"subject":[],"published":{"date-parts":[[2019,11]]},"assertion":[{"value":"2019-04-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-06-03","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-07-03","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}