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OGD increases the intracellular [AMP]\/[ATP] ratio, thereby activating the AMPK. In this study, we have investigated the involvement of NQO1 in OGD-mediated AMPK activation and cancer cell death. We found that OGD activates AMPK in an NQO1-dependent manner, suppressing the mTOR\/S6K\/4E-BP1 pathway, which is known to control cell survival. Thus, the depletion of NQO1 prevents AMPK-induced cancer cell death in OGD. When we blocked OGD-induced Ca<jats:sup>2+<\/jats:sup>\/CaMKII signaling, the NQO1-induced activation of AMPK was attenuated. In addition, when we blocked the RyR signaling, the accumulation of intracellular Ca<jats:sup>2+<\/jats:sup>and subsequent activation of CaMKII\/AMPK signaling was decreased in NQO1-expressing cells under OGD. Finally, siRNA-mediated knockdown of CD38 abrogated the OGD-induced activation of Ca<jats:sup>2+<\/jats:sup>\/CaMKII\/AMPK signaling. Taken together, we conclude that NQO1 plays a key role in the AMPK-induced cancer cell death in OGD through the CD38\/cADPR\/RyR\/Ca<jats:sup>2+<\/jats:sup>\/CaMKII signaling pathway.<\/jats:p>","DOI":"10.1038\/srep07769","type":"journal-article","created":{"date-parts":[[2015,1,14]],"date-time":"2015-01-14T10:15:53Z","timestamp":1421230553000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["NQO1-induced activation of AMPK contributes to cancer cell death by oxygen-glucose deprivation"],"prefix":"10.1038","volume":"5","author":[{"given":"Hyemi","family":"Lee","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eun-Taex","family":"Oh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo-Hwa","family":"Choi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moon-Taek","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ja-Kyeong","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae-Seon","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heon Joo","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2015,1,14]]},"reference":[{"key":"BFsrep07769_CR1","doi-asserted-by":"publisher","first-page":"5032","DOI":"10.1128\/MCB.14.8.5032","volume":"14","author":"WA Ausserer","year":"1994","unstructured":"Ausserer, W. 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