{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T13:57:46Z","timestamp":1768831066584,"version":"3.49.0"},"reference-count":30,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2011,4,12]],"date-time":"2011-04-12T00:00:00Z","timestamp":1302566400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Neuroscience Research"],"published-print":{"date-parts":[[2011,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Vitamin K (VK) has a protective effect on neural cells. Methylmercury is a neurotoxicant that directly induces neuronal death <jats:italic>in vivo<\/jats:italic> and <jats:italic>in vitro<\/jats:italic>. Therefore, in the present study, we hypothesized that VK inhibits the neurotoxicity of methylmercury. To prove our hypothesis <jats:italic>in vitro<\/jats:italic>, we investigated the protective effects of VKs (phylloquinone, vitamin K<jats:sub>1<\/jats:sub>; menaquinone\u20104, vitamin K<jats:sub>2<\/jats:sub>) on methylmercury\u2010induced death in primary cultured neurons from the cerebella of rat pups. As expected, VKs inhibited the death of the primary cultured neurons. It has been reported that the mechanisms underlying methylmercury toxicity involve a decrement of intracellular glutathione (GSH). Actually, treatment with GSH and a GSH inducer, N\u2010acetyl cysteine, inhibited methylmercury\u2010induced neuronal death in the present study. Thus, we investigated whether VKs also have protective effects against GSH\u2010depletion\u2010induced cell death by employing two GSH reducers, L\u2010buthionine sulfoximine (BSO) and diethyl maleate (DEM), in primary cultured neurons and human neuroblastoma IMR\u201032 cells. Treatment with VKs affected BSO\u2010 and DEM\u2010induced cell death in both cultures. On the other hand, the intracellular GSH assay showed that VK<jats:sub>2<\/jats:sub>, menaquinone\u20104, did not restore the reduced GSH amount induced by methylmercury or BSO treatments. These results indicate that VKs have the potential to protect neurons against the cytotoxicity of methylmercury and agents that deplete GSH, without increasing intracellular GSH levels. The protective effect of VKs may lead to the development of treatments for neural diseases involving GSH depletion. \u00a9 2011 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jnr.22630","type":"journal-article","created":{"date-parts":[[2011,4,12]],"date-time":"2011-04-12T14:29:49Z","timestamp":1302618589000},"page":"1052-1058","source":"Crossref","is-referenced-by-count":37,"title":["Vitamin K has the potential to protect neurons from methylmercury\u2010induced cell death <i>In Vitro<\/i>"],"prefix":"10.1002","volume":"89","author":[{"given":"Motoharu","family":"Sakaue","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naoko","family":"Mori","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maiko","family":"Okazaki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erika","family":"Kadowaki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takuya","family":"Kaneko","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natsuko","family":"Hemmi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hitomi","family":"Sekiguchi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takehiro","family":"Maki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aisa","family":"Ozawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuntaro","family":"Hara","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuyoshi","family":"Arishima","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masako","family":"Yamamoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2011,4,12]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1997.tb48445.x"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-0173(97)00045-3"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4547(20000315)59:6<775::AID-JNR10>3.0.CO;2-T"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0031-9384(85)90371-3"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF03033206"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0301-0082(99)00060-X"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1753-4887.1998.tb01753.x"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.8235659"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuro.2006.01.010"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1994.2461"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.23-13-05816.2003"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.22029"},{"key":"e_1_2_5_14_1","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1046\/j.1471-4159.1997.68062371.x","article-title":"Protection 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