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Ca<jats:sup>2+<\/jats:sup> permeable TRPM2 channel was gated by ADP-ribose (ADPR) and reactive oxygen species (ROS), although its activity was modulated in HYPX-exposed neurons by resveratrol (RSV). The aim of this study was to evaluate if a therapy of RSV can modulate the effect of HYPX in the TRPM2 expressing SH-SY5Y neuronal and HEK293 (no expression of TRPM2) cell lines. The SH-SY5Y and HEK293 cells were divided into four groups as control, RSV (50\u2009\u03bcM and 24\u2009hours), and HYPX and RSV\u2009+\u2009HYPX. For induction of HYPX in the cells, CoCl<jats:sub>2<\/jats:sub> (200\u2009\u03bcM and 24\u2009hours) incubation was used. HYPX-induced intracellular Ca<jats:sup>2+<\/jats:sup> responses to TRPM2 activation were increased in the SH-SY5Y cells but not in the HEK293 cells from coming H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> and ADPR. RSV treatment improved intracellular Ca<jats:sup>2+<\/jats:sup> responses, mitochondrial function, suppressed the generation of cytokine (IL-1\u03b2 and TNF-\u03b1), cytosolic and mitochondrial ROS in the SH-SY5Y cells. Intracellular free Zn<jats:sup>2+<\/jats:sup>, apoptosis, cell death, PARP-1, TRPM2 expression, caspase \u22123 and \u22129 levels are increased through activating TRPM2 in the SH-SY5Y cells exposed to the HYPX. However, the values were decreased in the cells by RSV and TRPM2 blockers (ACA and 2-APB). In SH-SY5Y neuronal cells exposed to HYPX conditions, the neuroprotective effects of RSV were shown to be exerted via modulation of oxidative stress, inflammation, apoptosis and death through modulation of TRPM2 channel. RSV could be used as an effective agent in the treatment of neurodegeneration exposure to HYPX.<\/jats:p>","DOI":"10.1038\/s41598-020-63577-5","type":"journal-article","created":{"date-parts":[[2020,4,15]],"date-time":"2020-04-15T10:03:12Z","timestamp":1586944992000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":92,"title":["Resveratrol attenuates hypoxia-induced neuronal cell death, inflammation and mitochondrial oxidative stress by modulation of TRPM2 channel"],"prefix":"10.1038","volume":"10","author":[{"given":"Yener","family":"Akyuva","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0887-6974","authenticated-orcid":false,"given":"Mustafa","family":"Naz\u0131ro\u011flu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,4,15]]},"reference":[{"key":"63577_CR1","doi-asserted-by":"publisher","unstructured":"Martini, S., Austin, T., Aceti, A., Faldella, G. & Corvaglia, L. 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