{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T02:35:42Z","timestamp":1747190142438,"version":"3.40.5"},"reference-count":64,"publisher":"American Physiological Society","issue":"4","funder":[{"name":"Chi Mei Medical Center, Tainan, Taiwan","award":["CMNDMC10809"],"award-info":[{"award-number":["CMNDMC10809"]}]}],"content-domain":{"domain":["journals.physiology.org"],"crossmark-restriction":true},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[2021,4,1]]},"abstract":"<jats:p> Disruption of copper homeostasis is closely involved in neurodegenerative disorders. This study examined whether a hybrid copper-binding compound, ( E)-2-(4-(dimethylamino)phenylimino)methyl)quinolin-8-ol (DPMQ), is able to protect NG108-15 cells against oxidative stress. We found that treatment of cells with rotenone or hydrogen peroxide increased cellular oxidative stress and resulted in mitochondrial dysfunction and apoptosis. The cellular levels of Nrf2 and the Cu<jats:sup>2+<\/jats:sup> chaperone DJ-1 were also decreased. These oxidative detrimental effects were all inhibited when cells were cotreated with DPMQ. DPMQ increased cellular Cu<jats:sup>2+<\/jats:sup> content, DJ-1 protein level, superoxide dismutase (SOD) activity, and Nrf2 nuclear translocation under basal state. The activity of SOD decreased under redox imbalance and this decrease was blocked by DPMQ treatment, while the protein level of SOD1 remained unaltered regardless of the oxidative stress and DPMQ treatment. Using endogenous proteins, coimmunoprecipitation showed that DJ-1 bound with SOD1 and Nrf2 individually. The amount of Nrf2, bound to DJ-1, consistently reflected its cellular level, while the amount of SOD1, bound to DJ-1, was potentiated by DPMQ, being greater in the basal state than under redox imbalance. Simultaneous inclusion of nonpermeable Cu<jats:sup>2+<\/jats:sup> chelator tetrathiomolybdate or triethylenetetramine during DPMQ treatment blocked all aforementioned effects of DPMQ, showing that the dependency of the effect of DPMQ on extracellular Cu<jats:sup>2+<\/jats:sup>. In addition, silencing of DJ-1 blocked the protection of DPMQ against oxidative stress. Taken all together, our results suggest that DPMQ stabilizes DJ-1 in a Cu<jats:sup>2+<\/jats:sup>-dependent manner, which then brings about SOD1 activation and Nrf2 nuclear translocation; these together alleviate cellular oxidative stress. <\/jats:p>","DOI":"10.1152\/ajpcell.00515.2019","type":"journal-article","created":{"date-parts":[[2020,12,23]],"date-time":"2020-12-23T18:44:13Z","timestamp":1608749053000},"page":"C635-C651","update-policy":"https:\/\/doi.org\/10.1152\/aps-crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Antioxidative effect of DJ-1 is enhanced in NG108-15 cells by DPMQ-induced copper influx"],"prefix":"10.1152","volume":"320","author":[{"given":"Ting-Yu","family":"Chin","sequence":"first","affiliation":[{"name":"Department of Bioscience Technology, Chung Yuan Christian University, Chungli, 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