{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T15:52:58Z","timestamp":1771602778520,"version":"3.50.1"},"reference-count":45,"publisher":"American Physiological Society","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Applied Physiology"],"published-print":{"date-parts":[[2008,1]]},"abstract":"<jats:p> Ribosomal S6 kinase 1 (S6K1) is a downstream component of the mammalian target of rapamycin (mTOR) signaling pathway and plays a regulatory role in translation initiation, protein synthesis, and muscle hypertrophy. AMP-activated protein kinase (AMPK) is a cellular energy sensor, a negative regulator of mTOR, and an inhibitor of protein synthesis. The purpose of this study was to determine whether the hypertrophy\/cell growth-associated mTOR pathway was downregulated during muscle atrophy associated with chronic paraplegia. Soleus muscle was collected from male Sprague-Dawley rats 10 wk following complete T<jats:sub>4<\/jats:sub>\u2013T<jats:sub>5<\/jats:sub> spinal cord transection (paraplegic) and from sham-operated (control) rats. We utilized immunoprecipitation and Western blotting techniques to measure upstream [AMPK, Akt\/protein kinase B (PKB)] and downstream components of the mTOR signaling pathway [mTOR, S6K1, SKAR, 4E-binding protein 1 (4E-BP1), and eukaryotic initiation factor (eIF) 4G and 2\u03b1]. Paraplegia was associated with significant soleus muscle atrophy (174 \u00b1 8 vs. 240 \u00b1 13 mg; P &lt; 0.05). There was a reduction in phosphorylation of mTOR, S6K1, and eIF4G ( P &lt; 0.05) with no change in Akt\/PKB or 4E-BP1 ( P &gt; 0.05). Total protein abundance of mTOR, S6K1, eIF2\u03b1, and Akt\/PKB was decreased, and increased for SKAR ( P &lt; 0.05), whereas 4E-BP1 and eIF4G did not change ( P &gt; 0.05). S6K1 activity was significantly reduced in the paraplegic group ( P &lt; 0.05); however, AMPK\u03b12 activity was not altered (3.5 \u00b1 0.4 vs. 3.7 \u00b1 0.5 pmol\u00b7mg<jats:sup>\u22121<\/jats:sup>\u00b7min<jats:sup>\u22121<\/jats:sup>, control vs. paraplegic rats). We conclude that paraplegia-induced muscle atrophy in rats is associated with a general downregulation of the mTOR signaling pathway. Therefore, in addition to upregulation of atrophy signaling during muscle wasting, downregulation of muscle cell growth\/hypertrophy-associated signaling appears to be an important component of long-term muscle loss. <\/jats:p>","DOI":"10.1152\/japplphysiol.00736.2007","type":"journal-article","created":{"date-parts":[[2007,9,21]],"date-time":"2007-09-21T00:58:48Z","timestamp":1190336328000},"page":"27-33","source":"Crossref","is-referenced-by-count":41,"title":["Chronic paraplegia-induced muscle atrophy downregulates the mTOR\/S6K1 signaling pathway"],"prefix":"10.1152","volume":"104","author":[{"given":"Hans C.","family":"Dreyer","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erin L.","family":"Glynn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heidi L.","family":"Lujan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher S.","family":"Fry","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen E.","family":"DiCarlo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Blake B.","family":"Rasmussen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00346.2003"},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1999.276.1.C120"},{"key":"R3","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.4.1.2136840"},{"key":"R4","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1101-1014"},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C200171200"},{"key":"R6","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C300534200"},{"key":"R7","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00733.2001"},{"key":"R8","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00253.2002"},{"key":"R9","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.2000.88.1.66"},{"key":"R10","doi-asserted-by":"publisher","DOI":"10.1007\/s004210000263"},{"key":"R11","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1990.68.1.48"},{"key":"R12","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.1989.00390080043011"},{"key":"R13","doi-asserted-by":"publisher","DOI":"10.1038\/sc.1992.158"},{"key":"R14","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1991.260.3.C528"},{"key":"R15","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2006.113175"},{"key":"R16","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1998.275.4.C1124"},{"key":"R17","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1207542"},{"key":"R18","doi-asserted-by":"publisher","DOI":"10.1042\/cs0720503"},{"key":"R19","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.68.1.913"},{"key":"R20","doi-asserted-by":"publisher","DOI":"10.1038\/ncb0203-87"},{"key":"R21","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.01113.2002"},{"key":"R22","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.1996.271.1.E50"},{"key":"R23","doi-asserted-by":"crossref","unstructured":"Hardie DG, Salt IP, Davies SP. 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