{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T14:05:51Z","timestamp":1789049151193,"version":"build-2803163510"},"reference-count":39,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2019,1,8]],"date-time":"2019-01-08T00:00:00Z","timestamp":1546905600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009101","name":"Henan Provincial Department of Education","doi-asserted-by":"publisher","award":["16IRTSTHN020"],"award-info":[{"award-number":["16IRTSTHN020"]}],"id":[{"id":"10.13039\/501100009101","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31471118"],"award-info":[{"award-number":["31471118"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Human neuroblastoma SH-SY5Y cells are a widely-used human neuronal cell model in the study of neurodegeneration. A recent study shows that, 1-methyl-4-phenylpyridine ion (MPP), which selectively causes dopaminergic neuronal death leading to Parkinson\u2019s disease-like symptoms, can reduce SH-SY5Y cell viability by inducing H2O2 generation and subsequent TRPM2 channel activation. MPP-induced cell death is enhanced by increasing the TRPM2 expression. By contrast, increasing the TRPM2 expression has also been reported to support SH-SY5Y cell survival after exposure to H2O2, leading to the suggestion of a protective role for the TRPM2 channel. To clarify the role of reactive oxygen species (ROS)-induced TRPM2 channel activation in SH-SY5Y cells, we generated a stable SH-SY5Y cell line overexpressing the human TRPM2 channel and examined cell death and cell viability after exposure to H2O2 in the wild-type and TRPM2-overexpressing SH-SY5Y cells. Exposure to H2O2 resulted in concentration-dependent cell death and reduction in cell viability in both cell types. TRPM2 overexpression remarkably augmented H2O2-induced cell death and reduction in cell viability. Furthermore, H2O2-induced cell death in both the wild-type and TRPM2-overexpressing cells was prevented by 2-APB, a TRPM2 inhibitor, and also by PJ34 and DPQ, poly(ADP-ribose) polymerase (PARP) inhibitors. Collectively, our results show that increasing the TRPM2 expression renders SH-SY5Y cells to be more susceptible to ROS-induced cell death and reinforce the notion that the TRPM2 channel plays a critical role in conferring ROS-induced cell death. It is anticipated that SH-SY5Y cells can be useful for better understanding the molecular and signaling mechanisms for ROS-induced TRPM2-mediated neurodegeneration in the pathogenesis of neurodegenerative diseases.<\/jats:p>","DOI":"10.3390\/cells8010028","type":"journal-article","created":{"date-parts":[[2019,1,10]],"date-time":"2019-01-10T03:22:31Z","timestamp":1547090551000},"page":"28","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Increasing the TRPM2 Channel Expression in Human Neuroblastoma SH-SY5Y Cells Augments the Susceptibility to ROS-Induced Cell Death"],"prefix":"10.3390","volume":"8","author":[{"given":"Xinfang","family":"An","sequence":"first","affiliation":[{"name":"Sino-UK Joint Laboratory for Brain Function and Injury and Department of Physiology and Neurobiology, Xinxiang Medical University, Xinxiang 453003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zixing","family":"Fu","sequence":"additional","affiliation":[{"name":"Sino-UK Joint Laboratory for Brain Function and Injury and Department of Physiology and Neurobiology, Xinxiang Medical University, Xinxiang 453003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chendi","family":"Mai","sequence":"additional","affiliation":[{"name":"Sino-UK Joint Laboratory for Brain Function and Injury and Department of Physiology and Neurobiology, Xinxiang Medical University, Xinxiang 453003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiming","family":"Wang","sequence":"additional","affiliation":[{"name":"Sino-UK Joint Laboratory for Brain Function and Injury and Department of Physiology and Neurobiology, Xinxiang Medical University, Xinxiang 453003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linyu","family":"Wei","sequence":"additional","affiliation":[{"name":"Sino-UK Joint Laboratory for Brain Function and Injury and Department of Physiology and Neurobiology, Xinxiang Medical University, Xinxiang 453003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongliang","family":"Li","sequence":"additional","affiliation":[{"name":"Sino-UK Joint Laboratory for Brain Function and Injury and Department of Physiology and Neurobiology, Xinxiang Medical University, Xinxiang 453003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaokun","family":"Li","sequence":"additional","affiliation":[{"name":"Sino-UK Joint Laboratory for Brain Function and Injury and Department of Physiology and Neurobiology, Xinxiang Medical University, Xinxiang 453003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6398-0411","authenticated-orcid":false,"given":"Lin-Hua","family":"Jiang","sequence":"additional","affiliation":[{"name":"Sino-UK Joint Laboratory for Brain Function and Injury and Department of Physiology and Neurobiology, Xinxiang Medical University, Xinxiang 453003, China"},{"name":"School of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, Leeds LS2 JT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,1,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1038\/nature02196","article-title":"TRP channels as cellular sensors","volume":"426","author":"Clapham","year":"2003","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1016\/S0092-8674(02)00670-0","article-title":"The TRP channels, a remarkably functional family","volume":"108","author":"Montell","year":"2002","journal-title":"Cell"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1146\/annurev.biochem.75.103004.142819","article-title":"TRP channels","volume":"76","author":"Venkatachalam","year":"2007","journal-title":"Annu. 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