{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T11:06:57Z","timestamp":1785928017178,"version":"3.56.0"},"reference-count":42,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2014,2,12]],"date-time":"2014-02-12T00:00:00Z","timestamp":1392163200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000923","name":"Australian Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000923","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004752","name":"State Government of Victoria","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004752","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2014,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    AMP\u2010activated protein kinase (AMPK) is a master regulator of metabolism. While Muscle\u2010specific AMPK \u03b21\u03b22 double\u2010knockout (\u03b21\u03b22M\u2010KO) mice display alterations in metabolic and mitochondrial capacity, their severe exercise intolerance suggested a secondary contributor to the observed phenotype. We find that tibialis anterior (TA), but not soleus, muscles of sedentary \u03b21\u03b22M\u2010KO mice display a significant myopathy (decreased myofiber areas, increased split and necrotic myofibers, and increased centrally nucleated myofibers. A mitochondrial\u2010 and fiber\u2010type\u2010specific etiology to the myopathy was ruled out. However, \u03b21\u03b22M\u2010KO TA muscles displayed significant (\n                    <jats:italic>P<\/jats:italic>\n                    &lt;0.05) increases in platelet aggregation and apoptosis within myofibers and surrounding interstitium (\n                    <jats:italic>P<\/jats:italic>\n                    &lt;0.05). These changes correlated with a 45% decrease in capillary density (\n                    <jats:italic>P<\/jats:italic>\n                    &lt;0.05). We hypothesized that the \u03b21\u03b22M\u2010KO myopathy in resting muscle resulted from impaired AMPK\u2010nNOS\u03bc signaling, causing increased platelet aggregation, impaired vasodilation, and, ultimately, ischemic injury. Consistent with this hypothesis, AMPK\u2010specific phosphorylation (Ser1446) of nNOS\u03bc was decreased in \u03b21\u03b22M\u2010KO compared to wild\u2010type (WT) mice. The AMPK\u2010nNOS\u03bc relationship was further demonstrated by administration of 5\u2010aminoimidazole\u20104\u2010carboxamide 1\u2010\u03b2\u2010D\u2010ribofuranoside (AICAR) to \u03b21\u03b22\u2010MKO muscles and C2C12 myotubes. AICAR significantly increased nNOS\u03bc phosphorylation and nitric oxide production (\n                    <jats:italic>P<\/jats:italic>\n                    &lt;0.05) within minutes of administration in WT muscles and C2C12 myotubes but not in \u03b21\u03b22M\u2010KO muscles. These findings highlight the importance of the AMPK\u2010nNOS\u03bc pathway in resting skeletal muscle.\u2014Thomas, M. M., Wang, D. C., D'Souza, D. M., Krause, M. P., Layne, A. S., Criswell, D. S., O'Neill, H. M., Connor, M. K., Anderson, J. E., Kemp, B. E., Steinberg, G. R., and Hawke, T. J. Musclespecific AMPK \u03b21\u03b22\u2010null mice display a myopathy due to loss of capillary density in nonpostural muscles.\n                    <jats:italic>FASEB J<\/jats:italic>\n                    . 28, 2098\u20132107 (2014).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.13-238972","type":"journal-article","created":{"date-parts":[[2014,2,13]],"date-time":"2014-02-13T01:02:50Z","timestamp":1392253370000},"page":"2098-2107","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Muscle\u2010specific AMPK \u03b21\u03b22\u2010null mice display a myopathy due to loss of capillary density in nonpostural muscles"],"prefix":"10.1096","volume":"28","author":[{"given":"Melissa M.","family":"Thomas","sequence":"first","affiliation":[{"name":"Department of Pathology and Molecular Medicine McMaster University Hamilton Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David C.","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pathology and Molecular Medicine McMaster University Hamilton Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donna M.","family":"D'Souza","sequence":"additional","affiliation":[{"name":"Department of Pathology and Molecular Medicine McMaster University Hamilton Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew P.","family":"Krause","sequence":"additional","affiliation":[{"name":"Department of Pathology and Molecular Medicine McMaster University Hamilton Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew S.","family":"Layne","sequence":"additional","affiliation":[{"name":"Center for Exercise Science Department of Applied Physiology and Kinesiology University of Florida Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David S.","family":"Criswell","sequence":"additional","affiliation":[{"name":"Center for Exercise Science Department of Applied Physiology and Kinesiology University of Florida Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hayley M.","family":"O'Neill","sequence":"additional","affiliation":[{"name":"St. Vincent's Institute of Medical Research University of Melbourne Fitzroy Victoria Australia"},{"name":"Department of Medicine University of Melbourne Fitzroy Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael K.","family":"Connor","sequence":"additional","affiliation":[{"name":"Muscle Health Research Centre York University Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judy E.","family":"Anderson","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences University of Manitoba Winnipeg Manitoba Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce E.","family":"Kemp","sequence":"additional","affiliation":[{"name":"St. Vincent's Institute of Medical Research University of Melbourne Fitzroy Victoria Australia"},{"name":"Department of Medicine University of Melbourne Fitzroy Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory R.","family":"Steinberg","sequence":"additional","affiliation":[{"name":"Department of Medicine McMaster University Hamilton Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas J.","family":"Hawke","sequence":"additional","affiliation":[{"name":"Department of Pathology and Molecular Medicine McMaster University Hamilton Ontario Canada"},{"name":"Muscle Health Research Centre York University Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,2,12]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00011.2008"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.056762"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.102434"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1105062108"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.53.12.3074"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.08-119057"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.10-155994"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2003.12.004"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0007293"},{"key":"e_1_2_7_11_1","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1080\/09537109777078","article-title":"PMA induces platelet activation of specific antigens (CD62\/CD63) in GpIIb-IIIa deficient platelets from Glanz-mann's thrombasthenia","volume":"8","author":"Baudouin-Brignole F.","year":"1997","journal-title":"Platelets"},{"key":"e_1_2_7_12_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.nmd.2006.12.005","article-title":"Commentary from the editor","volume":"17","author":"Dubowitz V.","year":"2007","journal-title":"Neuromuscul. Disord."},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10974-008-9155-8"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/0026-2862(68)90002-2"},{"key":"e_1_2_7_15_1","first-page":"H491","article-title":"A comparison of capillary hydraulic conductivities in postural and locomotor muscle","volume":"243","author":"McDonagh P. F.","year":"1982","journal-title":"Am. J. Physiol."},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2008.159871"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1139\/H07-079"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00382.2007"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.252625599"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00366.2006"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.01293.2009"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.021048"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.2000.279.5.E1202"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/372546a0"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.53.6.1429"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00101.2001"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.1997.273.1.E220"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0000806"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90471-9"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.184.2.609"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.01-0327com"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.hmg.a018926"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.250379497"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.1999.276.6.H1943"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.2174\/157016112798829760"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2009.00408.x"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature07414"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0003387"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI40736"},{"key":"e_1_2_7_40_1","first-page":"3","article-title":"Microcirculation in skeletal muscle","volume":"1","author":"Hudlicka O.","year":"2011","journal-title":"Muscles Ligaments Tendons J."},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2013.251082"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004410100449"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2004.076422"}],"container-title":["The FASEB Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.13-238972","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1096\/fj.13-238972","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.13-238972","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T20:59:28Z","timestamp":1761685168000},"score":1,"resource":{"primary":{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/10.1096\/fj.13-238972"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,2,12]]},"references-count":42,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2014,5]]}},"alternative-id":["10.1096\/fj.13-238972"],"URL":"https:\/\/doi.org\/10.1096\/fj.13-238972","archive":["Portico"],"relation":{},"ISSN":["0892-6638","1530-6860"],"issn-type":[{"value":"0892-6638","type":"print"},{"value":"1530-6860","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,2,12]]},"assertion":[{"value":"2013-08-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-01-23","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-02-12","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}