{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T15:17:51Z","timestamp":1781191071894,"version":"3.54.1"},"reference-count":68,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2017,7,3]],"date-time":"2017-07-03T00:00:00Z","timestamp":1499040000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008425","name":"Conseller\u00eda de Cultura, Educaci\u00f3n e Ordenaci\u00f3n Universitaria, Xunta de Galicia","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008425","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002924","name":"Federaci\u00f3n Espa\u00f1ola de Enfermedades Raras","doi-asserted-by":"publisher","award":["PI15\/01537"],"award-info":[{"award-number":["PI15\/01537"]}],"id":[{"id":"10.13039\/501100002924","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2017,12]]},"abstract":"Abstract<\/jats:title>Background<\/jats:title>Many pathological states characterized by muscle atrophy are associated with an increase in circulating glucocorticoids and poor patient prognosis, making it an important target for treatment. The development of treatments for glucocorticoid\u2010induced and wasting disorder\u2010related skeletal muscle atrophy should be designed based on how the particular transcriptional program is orchestrated and how the balance of muscle protein synthesis and degradation is deregulated. Here, we investigated whether the obestatin\/GPR39 system, an autocrine\/paracrine signaling system acting on myogenesis and with anabolic effects on the skeletal muscle, could protect against glucocorticoid\u2010induced muscle cell atrophy.<\/jats:p><\/jats:sec>Methods<\/jats:title>In the present study, we have utilized mouse C2C12 myotube cultures to examine whether the obestatin\/GPR39 signaling pathways can affect the atrophy induced by the synthetic glucocorticoid dexamethasone. We have extended these findings to in vitro<\/jats:italic> effects on human atrophy using human KM155C25 myotubes.<\/jats:p><\/jats:sec>Results<\/jats:title>The activation of the obestatin\/GPR39 system protects from glucocorticoid\u2010induced atrophy by regulation of Akt, PKD\/PKC\u03bc, CAMKII and AMPK signaling and its downstream targets in the control of protein synthesis, ubiquitin\u2013proteasome system and autophagy\u2013lysosome system in mouse cells. We compared mouse and human myotube cells in their response to glucocorticoid and identified differences in both the triggering of the atrophic program and the response to obestatin stimulation. Notably, we demonstrate that specific patterns of post\u2010translational modifications of FoxO4 and FoxO1 play a key role in directing FoxO activity in response to obestatin in human myotubes.<\/jats:p><\/jats:sec>Conclusions<\/jats:title>Our findings emphasize the function of the obestatin\/GPR39 system in coordinating a variety of pathways involved in the regulation of protein degradation during catabolic conditions.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcsm.12222","type":"journal-article","created":{"date-parts":[[2017,7,4]],"date-time":"2017-07-04T13:16:30Z","timestamp":1499174190000},"page":"974-990","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Obestatin controls the ubiquitin\u2013proteasome and autophagy\u2013lysosome systems in glucocorticoid\u2010induced muscle cell atrophy"],"prefix":"10.1002","volume":"8","author":[{"given":"Tania","family":"Cid\u2010D\u00edaz","sequence":"first","affiliation":[{"name":"\u00c1rea de Endocrinolog\u00eda Molecular y Celular, Instituto de Investigaci\u00f3n Sanitaria de Santiago (IDIS) Complejo Hospitalario Universitario de Santiago (CHUS), Servicio Gallego de Salud (SERGAS) Choupana s\/n 15706 Santiago de Compostela Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ic\u00eda","family":"Santos\u2010Zas","sequence":"additional","affiliation":[{"name":"\u00c1rea de Endocrinolog\u00eda Molecular y Celular, Instituto de Investigaci\u00f3n Sanitaria de Santiago (IDIS) Complejo Hospitalario Universitario de Santiago (CHUS), Servicio Gallego de Salud (SERGAS) Choupana s\/n 15706 Santiago de Compostela Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Gonz\u00e1lez\u2010S\u00e1nchez","sequence":"additional","affiliation":[{"name":"\u00c1rea de Endocrinolog\u00eda Molecular y Celular, Instituto de Investigaci\u00f3n Sanitaria de Santiago (IDIS) Complejo Hospitalario Universitario de Santiago (CHUS), Servicio Gallego de Salud (SERGAS) Choupana s\/n 15706 Santiago de Compostela Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ux\u00eda","family":"Gurriar\u00e1n\u2010Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Sprott Center for Stem Cell Research Ottawa Hospital Research Institute 501 Smyth Road Ottawa Ontario K1H 8L6 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos S.","family":"Mosteiro","sequence":"additional","affiliation":[{"name":"\u00c1rea de Endocrinolog\u00eda Molecular y Celular, Instituto de Investigaci\u00f3n Sanitaria de Santiago (IDIS) Complejo Hospitalario Universitario de Santiago (CHUS), Servicio Gallego de Salud (SERGAS) Choupana s\/n 15706 Santiago de Compostela Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xes\u00fas","family":"Casabiell","sequence":"additional","affiliation":[{"name":"Departamento de Fisiolog\u00eda Facultad de Veterinaria, Universidad de Santiago de Compostela (USC) Carballo Calero s\/n 27002 Lugo Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom\u00e1s","family":"Garc\u00eda\u2010Caballero","sequence":"additional","affiliation":[{"name":"Departamento de Ciencias Morfol\u00f3gicas Facultad de Medicina, USC San Francisco s\/n 15704 Santiago de Compostela Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Mouly","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9s, UPMC Universit\u00e9 Paris 06, INSERM UMRS974, CNRS FRE3617, Center for Research in Myology 47 Boulevard de l'h\u00f4pital 75013 Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yolanda","family":"Pazos","sequence":"additional","affiliation":[{"name":"\u00c1rea de Endocrinolog\u00eda Molecular y Celular, Instituto de Investigaci\u00f3n Sanitaria de Santiago (IDIS) Complejo Hospitalario Universitario de Santiago (CHUS), Servicio Gallego de Salud (SERGAS) Choupana s\/n 15706 Santiago de Compostela Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jes\u00fas P.","family":"Cami\u00f1a","sequence":"additional","affiliation":[{"name":"\u00c1rea de Endocrinolog\u00eda Molecular y Celular, Instituto de Investigaci\u00f3n Sanitaria de Santiago (IDIS) Complejo Hospitalario Universitario de Santiago (CHUS), Servicio Gallego de Salud (SERGAS) Choupana s\/n 15706 Santiago de Compostela Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,7,3]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm0604-584"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00204.2014"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.91355.2008"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.03.017"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1152\/physiol.00041.2007"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2007.11.001"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2010.01.056"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb0203-87"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(04)00400-3"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature06639"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2014.02.003"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2007.11.004"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2012.84"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20091346"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms7670"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.09.004"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1164265"},{"key":"e_1_2_7_19_1","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1016\/S0021-9258(17)43531-9","article-title":"Glucocorticoid\u2010receptor complexes in rat thymus cells. Rapid kinetic behavior and a cyclic model","volume":"259","author":"Munck A","year":"1984","journal-title":"J Biol Chem"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.CCM.0000279194.11328.77"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2008-0439"},{"key":"e_1_2_7_22_1","first-page":"3059","article-title":"Endogenous glucocorticoids and impaired insulin signaling are both required to stimulate muscle wasting under pathophysiological conditions in mice","volume":"119","author":"Hu Z","year":"2009","journal-title":"J Clin Invest"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(04)00211-4"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2011.01.001"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.374926"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2015.40"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-015-1994-z"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1101-1014"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M407517200"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1186\/2044-5040-1-34"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13395-016-0115-5"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2012.09.003"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.010389"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2013.05.036"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2008.21"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0400373101"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0090398"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1369\/jhc.2010.956201"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/stem.1158"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0042166"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo-89-1-96"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1677\/joe.0.0620341"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1988.65.1.173"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.ph.57.030195.001203"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2249"},{"key":"e_1_2_7_46_1","doi-asserted-by":"crossref","first-page":"2308","DOI":"10.1016\/S0021-9258(19)85891-X","article-title":"Regulation of rat liver acetyl\u2010CoA carboxylase. Regulation of phosphorylation and inactivation of acetyl\u2010CoA carboxylase by the adenylate energy charge","volume":"255","author":"Yeh LA","year":"1980","journal-title":"J Biol Chem"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI19874"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0405454101"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M213069200"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1934283100"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0406789102"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/35040593"},{"key":"e_1_2_7_53_1","first-page":"4131","article-title":"Signaling chromatin to make muscle. Curr Opin Cell Biol. 2002; 14: 763\u2010772.5264 Potthoff MJ, Olson EN. MEF2: a central regulator of diverse developmental programs","volume":"134","author":"McKinsey TA","year":"2007","journal-title":"Development"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.24.19.8374-8385.2004"},{"key":"e_1_2_7_55_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20042034"},{"key":"e_1_2_7_56_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M413396200"},{"key":"e_1_2_7_57_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI27438"},{"key":"e_1_2_7_58_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1094637"},{"key":"e_1_2_7_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(04)00126-6"},{"key":"e_1_2_7_60_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0400593101"},{"key":"e_1_2_7_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2007.07.003"},{"key":"e_1_2_7_62_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0712145105"},{"key":"e_1_2_7_63_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb2069"},{"key":"e_1_2_7_64_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2015.193"},{"key":"e_1_2_7_65_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.140228"},{"key":"e_1_2_7_66_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0601565103"},{"key":"e_1_2_7_67_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.03-0610com"},{"key":"e_1_2_7_68_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.06-6604com"},{"key":"e_1_2_7_69_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12089"}],"container-title":["Journal of Cachexia, Sarcopenia and Muscle"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjcsm.12222","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcsm.12222","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,15]],"date-time":"2023-09-15T19:42:30Z","timestamp":1694806950000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcsm.12222"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,7,3]]},"references-count":68,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2017,12]]}},"alternative-id":["10.1002\/jcsm.12222"],"URL":"https:\/\/doi.org\/10.1002\/jcsm.12222","archive":["Portico"],"relation":{},"ISSN":["2190-5991","2190-6009"],"issn-type":[{"value":"2190-5991","type":"print"},{"value":"2190-6009","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,7,3]]},"assertion":[{"value":"2016-12-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-05-22","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-07-03","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}