{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T05:28:27Z","timestamp":1764048507572,"version":"3.45.0"},"reference-count":39,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2021,5,13]],"date-time":"2021-05-13T00:00:00Z","timestamp":1620864000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","award":["BB\/J01754X\/1"],"award-info":[{"award-number":["BB\/J01754X\/1"]}],"id":[{"id":"10.13039\/501100000268","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":[[2021,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Skeletal muscle mass and function are partly maintained by the supply of amino acids, altered amino acid transport is an important cause of frailty that can lead to decreased independence with increasing age and slow trauma recovery. The system\u2010A sodium coupled neutral amino acid transporter (SNAT)\u20102 coded by gene family SLC38A2 generates a 506 amino acid 56\u00a0kDa protein that is an important transporter of amino acids in skeletal muscle. Ageing is associated with a decrease in expression of SNAT2 transporters.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this study, we used the C2C12 cell line, using myoblast cells and cells differentiated into myotubes. We investigated if the expression of SNAT2 DNA would enhance intracellular amino acid levels and increase their availability for protein synthesis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In control myoblasts and myotubes, we found significantly decreased expression of SNAT2 (6.5\u00d7 decrease,\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a04 per group,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a00.05) in myotubes than found in myoblasts. After transfection with a SNAT2\u2010eGFP cDNA plasmid, C2C12 myoblasts significantly increased perinuclear punctate SNAT2\u2010eGFP expression that persisted and was more cytoplasmic after differentiation into myotubes. Interestingly, transfected cells were significantly more responsive to the hormone 5\u03b1\u2010dihydrotestosterone (DHT, 4.5\u00a0nM, by 1.6\u00d7,\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a03 per group,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a00.04). Starvation significantly enhanced the amino acid C\n                      <jats:sup>14<\/jats:sup>\n                      \u2010MeAIB transport (1.7\u00d7,\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a03 per group,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a00.05) indicating increased function of SNAT2. Inhibiting SNAT2 with high concentrations of MeAIB (3.3 or 5\u00a0mM) significantly reduced C\n                      <jats:sup>14<\/jats:sup>\n                      \u2010Isoleucine transport by L\u2010type amino acid transporter (LAT2, 52.8% and 77%, respectively,\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a03 per group,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a00.05). However, there was no increase in the LAT2 transport of C\n                      <jats:sup>14<\/jats:sup>\n                      \u2010isoleucine detectable in SNAT2\u2010eGFP transfected cells after DHT (4.5\u00a0nM) exposure. This indicated that small amino acid availability was not rate limiting to LAT2 function in myoblasts.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Overall, these data show that transfection of SNAT2\u2010eGFP expression enhanced its function following starvation and treatment with physiological levels of DHT. Enhanced SNAT2 expression in muscle cells offers a viable epigenetic target in pathological conditions associated with altered amino acid transport.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcsm.12707","type":"journal-article","created":{"date-parts":[[2021,5,13]],"date-time":"2021-05-13T05:42:11Z","timestamp":1620884531000},"page":"811-822","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Enhanced small neutral but not branched chain amino acid transport after epigenetic sodium coupled neutral amino acid transporter\u20102 (SNAT2) cDNA expression in myoblasts"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3653-4421","authenticated-orcid":false,"given":"Timothy","family":"Pearson","sequence":"first","affiliation":[{"name":"Biomedical Research Centre, Norwich Medical School University of East Anglia  Norwich UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oskar","family":"Wendowski","sequence":"additional","affiliation":[{"name":"Biomedical Research Centre, Norwich Medical School University of East Anglia  Norwich UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5347-0490","authenticated-orcid":false,"given":"Penny P.","family":"Powell","sequence":"additional","affiliation":[{"name":"Biomedical Research Centre, Norwich Medical School University of East Anglia  Norwich UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,5,13]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2772"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.1999.277.3.E513"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0838.1995.tb00026.x"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-510X(88)90132-3"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1067\/mlc.2001.113504"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2014.10.505"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10522-018-9770-8"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11357-016-9937-7"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exger.2010.08.029"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.mjt.0000132252.80403.c9"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.ircmb.2019.03.003"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.pmbts.2015.06.015"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/glp097"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/0047-6374(91)90131-I"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00726-012-1326-7"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.91002.2008"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2013.253203"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12122"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M108609200"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2018.06.018"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00019.2003"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-0436.1977.tb01507.x"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1159\/000016776"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.ctdb.2017.08.002"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nucmedbio.2017.01.008"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40634-016-0051-7"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1962212"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2018.00063"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00603.2011"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj3550563"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1748-1716.2006.01552.x"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M600341200"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00726-008-0050-9"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3351"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)35969-0"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.04-2640fje"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1249\/mss.0b013e31815bbba9"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0005-2736(00)00390-4"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12501"}],"container-title":["Journal of Cachexia, Sarcopenia and Muscle"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcsm.12707","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jcsm.12707","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcsm.12707","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T03:36:52Z","timestamp":1764041812000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcsm.12707"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,13]]},"references-count":39,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2021,6]]}},"alternative-id":["10.1002\/jcsm.12707"],"URL":"https:\/\/doi.org\/10.1002\/jcsm.12707","archive":["Portico"],"relation":{},"ISSN":["2190-5991","2190-6009"],"issn-type":[{"type":"print","value":"2190-5991"},{"type":"electronic","value":"2190-6009"}],"subject":[],"published":{"date-parts":[[2021,5,13]]},"assertion":[{"value":"2020-12-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-03-29","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-05-13","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}