{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T02:20:05Z","timestamp":1791339605155,"version":"4.3.1"},"reference-count":43,"publisher":"American Physiological Society","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2011,1]]},"abstract":"<jats:p> The present study determined whether AMP-activated protein kinase (AMPK) regulates heme oxygenase (HO)-1 gene expression in endothelial cells (ECs) and if HO-1 contributes to the biological actions of this kinase. Treatment of human ECs with the AMPK activator 5-aminoimidazole-4-carboxamide-1-\u03b2-d-ribofuranoside (AICAR) stimulated a concentration- and time-dependent increase in HO-1 protein and mRNA expression that was associated with a prominent increase in nuclear factor-erythroid 2-related factor 2 (Nrf2) protein. Induction of HO-1 was also observed in rat carotid arteries after the in vivo application of AICAR. Induction of HO-1 by AICAR was blocked by the AMPK inhibitor compound C, the adenosine kinase inhibitor 5\u2032-iodotubercidin, and by silencing AMPK-\u03b1<jats:sub>1\/2<\/jats:sub> and was mimicked by the AMPK activator A-769662 and by infecting ECs with an adenovirus expressing constitutively active AMPK-\u03b1<jats:sub>1<\/jats:sub>. AICAR also induced a significant rise in HO-1 promoter activity that was abolished by mutating the antioxidant responsive elements of the HO-1 promoter or by the overexpression of dominant negative Nrf2. Finally, activation of AMPK inhibited cytokine-mediated EC death, and this was prevented by the HO inhibitor tin protoporphyrin-IX or by silencing HO-1 expression. In conclusion, AMPK stimulates HO-1 gene expression in human ECs via the Nrf2\/antioxidant responsive element signaling pathway. The induction of HO-1 mediates the antiapoptotic effect of AMPK, and this may provide an important adaptive response to preserve EC viability during periods of metabolic stress. <\/jats:p>","DOI":"10.1152\/ajpheart.00749.2010","type":"journal-article","created":{"date-parts":[[2010,10,30]],"date-time":"2010-10-30T20:14:43Z","timestamp":1288469683000},"page":"H84-H93","source":"Crossref","is-referenced-by-count":148,"title":["Activation of AMPK stimulates heme oxygenase-1 gene expression and human endothelial cell survival"],"prefix":"10.1152","volume":"300","author":[{"given":"Xiao-ming","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Medical Pharmacology and Physiology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly J.","family":"Peyton","sequence":"additional","affiliation":[{"name":"Department of Medical Pharmacology and Physiology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmad R.","family":"Shebib","sequence":"additional","affiliation":[{"name":"Department of Medical Pharmacology and Physiology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Temple University School of Medicine, Philadelphia, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald J.","family":"Korthuis","sequence":"additional","affiliation":[{"name":"Department of Medical Pharmacology and Physiology and"},{"name":"Dalton Cardiovascular Research Center, University of Missouri, Columbia, Missouri; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Durante","sequence":"additional","affiliation":[{"name":"Department of Medical Pharmacology and Physiology and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2006-0340TR"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.192.7.1015"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.51.7.2199"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2006.09.018"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.108.187567"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20090613"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1995.tb20498.x"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.55.02.06.db05-1064"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20061609"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1111\/j.1582-4934.2006.tb00427.x"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.78.6.1075"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.108.175919"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.109.201590"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1080\/10739680802355897"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00744.2006"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M706536200"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1997.00259.x"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.0000221429.94591.72"},{"key":"B19","first-page":"71","volume":"23","author":"Henderson JF","year":"1972","journal-title":"Cancer Chemother Rep"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.51.1.159"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1042\/bst0310162"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/28.7.1003"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.55.01.06.db05-0943"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.2337\/db08-1512"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.107.160085"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2007.03.004"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M212831200"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2009.04.007"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1038\/hr.2008.25"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M300643200"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000136025.96811.76"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2009.05.008"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.108.183392"},{"key":"B34","first-page":"441","volume":"51","author":"Peyton KJ","year":"2002","journal-title":"Blood"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.108.784289"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M209195200"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0006588"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2008.02.126"},{"key":"B39","doi-asserted-by":"crossref","first-page":"1893","DOI":"10.2337\/db09-0267","volume":"58","author":"Xie Z","year":"2009","journal-title":"Diabetes"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.164.9.4665"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1172\/JCI13505"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1111\/j.1748-1716.2009.01967.x"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1681.2007.04851.x"}],"container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/ajpheart.00749.2010","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,9,8]],"date-time":"2019-09-08T16:59:16Z","timestamp":1567961956000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajpheart.00749.2010"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,1]]},"references-count":43,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2011,1]]}},"alternative-id":["10.1152\/ajpheart.00749.2010"],"URL":"https:\/\/doi.org\/10.1152\/ajpheart.00749.2010","relation":{},"ISSN":["0363-6135","1522-1539"],"issn-type":[{"value":"0363-6135","type":"print"},{"value":"1522-1539","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,1]]}}}