{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T00:46:00Z","timestamp":1772585160425,"version":"3.50.1"},"reference-count":53,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2018,6,26]],"date-time":"2018-06-26T00:00:00Z","timestamp":1529971200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100006578","name":"Chi Mei Medical Center","doi-asserted-by":"publisher","award":["CMNDMC10605"],"award-info":[{"award-number":["CMNDMC10605"]}],"id":[{"id":"10.13039\/501100006578","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003559","name":"Ministry of National Defense","doi-asserted-by":"publisher","award":["MAB\u2010106\u2010073"],"award-info":[{"award-number":["MAB\u2010106\u2010073"]}],"id":[{"id":"10.13039\/501100003559","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2018,12]]},"abstract":"<jats:p>Copper is more likely than iron to generate reactive oxygen species (ROS) in a redox reaction due to its higher electrochemical reactivity. This study examined the effect of a newly synthesized Cu<jats:sup>2+<\/jats:sup> binding compound, (<jats:italic>E<\/jats:italic>)\u20102\u2010(4\u2010(dimethylamino)phenylimino)methyl)quinolin\u20108\u2010ol (DPMQ), on ultraviolet B (UVB) irradiation\u2013induced cytotoxicity in human dermal fibroblasts. DPMQ induced Cu<jats:sup>2+<\/jats:sup> influx as effectively as disulfiram, a Cu<jats:sup>2+<\/jats:sup> ionophore anticancer drug. However, disulfiram induced ROS generation, mitochondrial dysfunction, and apoptosis in fibroblasts in a Cu<jats:sup>2+<\/jats:sup>\u2010dependent manner, whereas DPMQ was not only nontoxic, but protected cells against UVB irradiation\u2013induced apoptosis in a Cu<jats:sup>2+<\/jats:sup>\u2010independent manner. UVB irradiation induced a Ca<jats:sup>2+<\/jats:sup>\u2010dependent increase in ROS generation, a decrease in Nrf2 levels, and activation of the mitochondrial apoptotic pathway, and these effects were prevented by DPMQ, which also increased Nrf2 nuclear translocation in a Cu<jats:sup>2+<\/jats:sup>\u2010independent manner. UVB irradiation activated 12\u2010lipoxygenase and 12\u2010hydroxyeicosatetraenoic acid (12\u2010HETE), a product of 12\u2010lipoxygenase, activated the TRPV1 channel. DMPQ did not act as a Ca<jats:sup>2+<\/jats:sup> chelator, but inhibited the cytosolic Ca<jats:sup>2+<\/jats:sup> increase induced by 12\u2010HETE or capsaicin, but not that induced by bradykinin or ATP. Blockade of Ca<jats:sup>2+<\/jats:sup> influx by pharmacological inhibition or silencing of the TRPV1 channel or chelation of cytosolic Ca<jats:sup>2+<\/jats:sup> inhibited the UVB irradiation\u2013induced Nrf2 reduction, ROS generation, mitochondrial dysfunction, and apoptosis. Taken together, our results suggest that Ca<jats:sup>2+<\/jats:sup> influx via the TRPV1 channel is responsible for UVB irradiation\u2013induced cytotoxicity and that DPMQ protects cells against UVB irradiation by inhibiting the TRPV1 channel and stabilizing Nrf2, and could thus be a potentially useful compound for the treatment of free radical\u2010induced diseases.<\/jats:p>","DOI":"10.1002\/jcp.26861","type":"journal-article","created":{"date-parts":[[2018,6,26]],"date-time":"2018-06-26T10:33:37Z","timestamp":1530009217000},"page":"9594-9610","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["A new copper ionophore DPMQ protects cells against ultraviolet B irradiation by inhibiting the TRPV1 channel"],"prefix":"10.1002","volume":"233","author":[{"given":"Kuo\u2010Feng","family":"Huang","sequence":"first","affiliation":[{"name":"Division of Plastic Surgery, Department of Surgery Chi Mei Medical Center  Tainan Taiwan Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kuo\u2010Hsing","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Biology and Anatomy National Defense Medical Center  Taipei Taiwan Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu\u2010Chien","family":"Hung","sequence":"additional","affiliation":[{"name":"Department of Biochemistry National Defense Medical Center  Taipei Taiwan Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liang\u2010Chuan","family":"Lo","sequence":"additional","affiliation":[{"name":"Department of Biochemistry National Defense Medical Center  Taipei Taiwan Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kuo\u2010Chen","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Biochemistry National Defense Medical Center  Taipei Taiwan Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pei\u2010Shan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Microbiology Soochow University  Taipei Taiwan Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ming\u2010Kuan","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry School of Pharmacy, National Defense Medical Center  Taipei Taiwan Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9741-3017","authenticated-orcid":false,"given":"Sheau\u2010Huei","family":"Chueh","sequence":"additional","affiliation":[{"name":"Department of Biochemistry National Defense Medical Center  Taipei Taiwan Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,6,26]]},"reference":[{"key":"e_1_2_7_1_2_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00299.2003"},{"key":"e_1_2_7_1_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2007.04582.x"},{"key":"e_1_2_7_1_4_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M310268200"},{"key":"e_1_2_7_1_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1755-5949.2010.00231.x"},{"key":"e_1_2_7_1_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2011.02.006"},{"key":"e_1_2_7_1_7_1","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1158\/1535-7163.1049.3.9","article-title":"Disulfiram inhibits activating transcription factor\/cyclic AMP\u2010responsive element binding protein and human melanoma growth in a metal\u2010dependent manner in vitro, in mice and in a patient with metastatic disease","volume":"3","author":"Brar S. 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