{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T00:22:42Z","timestamp":1777422162812,"version":"3.51.4"},"reference-count":34,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2012,8,23]],"date-time":"2012-08-23T00:00:00Z","timestamp":1345680000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2012,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The proline hydroxylase domain\u2010containing enzymes (PHD) act as cellular oxygen sensors and initiate a hypoxic signal cascade to induce a range of cellular responses to hypoxia especially in the aspect of energy and metabolic homeostasis regulation. AMP\u2010activated protein kinase (AMPK) is recognized as a major energetic sensor and regulator of cardiac metabolism. However, the effect of PHD signal on AMPK has never been studied before. A PHD inhibitor (PHI), dimethyloxalylglycine and PHD2\u2010specific RNA interference (RNAi) have been used to activate PHD signalling in neonatal rat cardiomyocytes. Both PHI and PHD2\u2010RNAi activated AMPK pathway in cardiomyocytes effectively. In addition, the increased glucose uptake during normoxia and enhanced myocyte viability during hypoxia induced by PHI pretreatment were abrogated substantially upon AMPK inhibition with an adenoviral vector expressing a dominant negative mutant of AMPK\u2010\u03b11. Furthermore, chelation of intracellular Ca2+ by BAPTA, inhibition of calmodulin\u2010dependent kinase kinase (CaMKK) with STO\u2010609, or RNAi\u2010mediated down\u2010regulation of CaMKK \u03b1 inhibited PHI\u2010induced AMPK activation significantly. In contrast, down\u2010regulation of LKB1 with adenoviruses expressing the dominant negative form did not affect PHI\u2010induced AMPK activation. We establish for the first time that activation of PHD signal cascade can activate AMPK pathway mainly through a Ca<jats:sup>2+<\/jats:sup>\/CaMKK\u2010dependent mechanism in cardiomyocytes. Furthermore, activation of AMPK plays an essential role in hypoxic protective responses induced by PHI.<\/jats:p>","DOI":"10.1111\/j.1582-4934.2011.01500.x","type":"journal-article","created":{"date-parts":[[2011,12,1]],"date-time":"2011-12-01T16:23:55Z","timestamp":1322756635000},"page":"2049-2059","source":"Crossref","is-referenced-by-count":25,"title":["Activation of the prolyl\u2010hydroxylase oxygen\u2010sensing signal cascade leads to AMPK activation in cardiomyocytes"],"prefix":"10.1111","volume":"16","author":[{"given":"Hong","family":"Yan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dong\u2010Xia","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaohua","family":"Shi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yue\u2010Sheng","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2012,8,23]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1066373"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-08-0074"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1059817"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0436037100"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0602235103"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M511408200"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M301391200"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2007.04873.x"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00100.2006"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200422683"},{"key":"e_1_2_7_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2004.12.003"},{"key":"e_1_2_7_13_2","doi-asserted-by":"crossref","unstructured":"BaronSJ LiJ RussellRR et al.Dual mechanisms regulating AMPK kinase action in the ischemic heart. 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