{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T09:55:15Z","timestamp":1790848515604,"version":"4.1.0"},"reference-count":31,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T00:00:00Z","timestamp":1772064000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T00:00:00Z","timestamp":1772064000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100020950","name":"National Science and Technology Council","doi-asserted-by":"publisher","award":["NSTC 114\u20102320\u2010B\u2010075B\u2010001\u2010MY3"],"award-info":[{"award-number":["NSTC 114\u20102320\u2010B\u2010075B\u2010001\u2010MY3"]}],"id":[{"id":"10.13039\/501100020950","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Applied Toxicology"],"published-print":{"date-parts":[[2026,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Alternariol (AOH) is a low\u2010molecular\u2010weight mycotoxin produced by\n                    <jats:italic>Alternaria<\/jats:italic>\n                    species, frequently found in cereal grains, tomatoes, and processed foods. While its genotoxic and endocrine\u2010disrupting effects are well established, emerging studies suggest a neurotoxic potential that remains poorly understood. Astrocytes\u2014key regulators of neuronal support and calcium (Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ) balance in the central nervous system (CNS)\u2014are an underexplored target of AOH toxicity. Here, we investigated the effects of AOH on Ca\n                    <jats:sup>2+<\/jats:sup>\n                    signaling and viability in human astrocytes (Gibco Human Astrocyte, GHA cells). AOH exposure (25\u2013125\u2009\u03bcM) caused a concentration\u2010dependent rise in cytosolic Ca\n                    <jats:sup>2+<\/jats:sup>\n                    concentrations ([Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ]\u1d62) and induced significant cytotoxicity. These effects were reversed by the intracellular Ca\n                    <jats:sup>2+<\/jats:sup>\n                    chelator BAPTA\u2010AM, suggesting a Ca\n                    <jats:sup>2+<\/jats:sup>\n                    \u2010dependent mechanism. Mechanistically, AOH mobilized Ca\n                    <jats:sup>2+<\/jats:sup>\n                    from the endoplasmic reticulum (ER), as shown by thapsigargin blockade, and facilitated extracellular influx via store\u2010operated calcium entry (SOCE), inhibited by 2\u2010APB (a SOCE inhibitor) and GF109203X (a protein kinase C, PKC inhibitor). Notably, inhibition of phospholipase C (PLC) by U73122 completely abolished the Ca\n                    <jats:sup>2+<\/jats:sup>\n                    rise, implicating the PLC\u2013ER axis as a key upstream trigger. Together, our findings reveal a novel Ca\n                    <jats:sup>2+<\/jats:sup>\n                    \u2010dependent mechanism by which AOH disrupts astrocyte homeostasis, providing new insights into its neurotoxic potential and highlighting Ca\n                    <jats:sup>2+<\/jats:sup>\n                    signaling as a potential therapeutic target in glial toxicology.\n                  <\/jats:p>","DOI":"10.1002\/jat.70054","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T17:49:52Z","timestamp":1772992192000},"page":"3703-3715","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Mycotoxin Alternariol Induces Ca\n                    <sup>2+<\/sup>\n                    Dysregulation and Cell Death in Astrocytes: Mechanistic Toxicological Insights"],"prefix":"10.1002","volume":"46","author":[{"given":"Ying\u2010Tso","family":"Chen","sequence":"first","affiliation":[{"name":"Graduate Institute of Clinical Medicine, College of Medicine Kaohsiung Medical University  Kaohsiung Taiwan"},{"name":"Department of Neurosurgery Kaohsiung Veterans General Hospital  Kaohsiung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei\u2010Chih","family":"Sun","sequence":"additional","affiliation":[{"name":"Institution of Biomedical Sciences National Sun Yat\u2010Sen University  Kaohsiung Taiwan"},{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine Kaohsiung Veterans General Hospital  Kaohsiung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Che\u2010Sheng","family":"Chu","sequence":"additional","affiliation":[{"name":"Graduate Institute of Clinical Medicine, College of Medicine Kaohsiung Medical University  Kaohsiung Taiwan"},{"name":"Department of Psychiatry Kaohsiung Veterans General Hospital  Kaohsiung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7131-6377","authenticated-orcid":false,"given":"Wei\u2010Zhe","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Medical Education and Research Kaohsiung Veterans General Hospital  Kaohsiung Taiwan"},{"name":"Department of Pharmacy and Master Program, College of Pharmacy and Health Care Tajen University  Pingtung County Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,2,26]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/1541\u20104337.12803"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.mcb.2017.07.002"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4201"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2017.01.098"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a038802"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018\u2010013\u20101550\u20107"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.11.028"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018\u2010023\u201005023\u2010z"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxlet.2024.02.008"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12550\u2010010\u20100063\u20106"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/femsre\/fuad061"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.etap.2022.103965"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrestox.1c00364"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells9010160"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)83641-4"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.foodchem.2024.142064"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines11020357"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.3390\/jof9030282"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.22673"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nurt.2010.07.006"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2022.113524"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1080\/19440049.2023.2294003"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.3390\/toxins12090595"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471\u20104159.2012.07664.x"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00204\u2010024\u201003743\u20100"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcpt.12635"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mrgentox.2021.503435"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/1541\u20104337.70085"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035\u2010015\u20109485\u20107"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.3390\/toxins15030201"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1042\/AN20110061"}],"container-title":["Journal 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