{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T17:01:36Z","timestamp":1788800496515,"version":"build-2803163510"},"reference-count":34,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2011,10,3]],"date-time":"2011-10-03T00:00:00Z","timestamp":1317600000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2011,11]]},"abstract":"<jats:sec><jats:label\/><jats:p><jats:italic>J. Neurochem.<\/jats:italic>(2011)<jats:bold>119<\/jats:bold>, 839\u2013847.<\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>Chloroquine, a widely used anti\u2010malarial and anti\u2010rheumatoid agent, has been reported to induce apoptotic and non\u2010apoptotic cell death. Accumulating evidence now suggests that chloroquine can sensitize cancer cells to cell death and augment chemotherapy\u2010induced apoptosis by inhibiting autophagy. However, chloroquine is reported to induce GM1 ganglioside accumulation in cultured cells at low \u03bcM concentrations and prevent damage to the blood brain barrier in mice. It remains unknown whether chloroquine has neuroprotective properties at concentrations below its reported ability to inhibit lysosomal enzymes and autophagy. In the present study, we demonstrated that chloroquine protected mouse hippocampal HT22 cells from glutamate\u2010induced oxidative stress by attenuating production of excess reactive oxygen species. The concentration of chloroquine required to rescue HT22 cells from oxidative stress was much lower than that sufficient enough to induce cell death and inhibit autophagy. Chloroquine increased GM1 level in HT22 cells at low \u03bcM concentrations but glutamate\u2010induced cell death occurred before GM1 accumulation, suggesting that GM1 induction is not related to the protective effect of chloroquine against glutamate\u2010induced cell death. Interestingly, BD1047 and NE\u2010100, sigma\u20101 receptor antagonists, abrogated the protective effect of chloroquine against glutamate\u2010induced cell death and reactive oxygen species production. In addition, cutamesine (SA4503), a sigma\u20101 receptor agonist, prevented both glutamate\u2010induced cell death and reactive oxygen species production. These findings indicate that chloroquine at concentrations below its ability to inhibit autophagy and induce cell death is able to rescue HT22 cells from glutamate\u2010induced cell death by reducing excessive production of reactive oxygen species through sigma\u20101 receptors. These results suggest potential use of chloroquine, an established anti\u2010malarial agent, as a neuroprotectant against oxidative stress, which occurs in a variety of neurodegenerative diseases.<\/jats:p><\/jats:sec>","DOI":"10.1111\/j.1471-4159.2011.07464.x","type":"journal-article","created":{"date-parts":[[2011,9,1]],"date-time":"2011-09-01T04:45:41Z","timestamp":1314852341000},"page":"839-847","source":"Crossref","is-referenced-by-count":58,"title":["Chloroquine inhibits glutamate\u2010induced death of a neuronal cell line by reducing reactive oxygen species through sigma\u20101 receptor"],"prefix":"10.1111","volume":"119","author":[{"given":"Yoko","family":"Hirata","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideko","family":"Yamamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mostafa Shukry Moursy","family":"Atta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shawky","family":"Mahmoud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kentaro","family":"Oh\u2010hashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazutoshi","family":"Kiuchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2011,10,3]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s007020070082"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm900227u"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1166127"},{"key":"e_1_2_7_5_1","first-page":"473","article-title":"Chloroquine\u2010induced autophagic vacuole accumulation and cell death in glioma cells is p53 independent","volume":"12","author":"Geng Y.","year":"2010","journal-title":"Neuro Oncol."},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2009.03.067"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1998.70041335.x"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.08.036"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(76)90326-2"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3940(98)00943-4"},{"key":"e_1_2_7_11_1","first-page":"1269","article-title":"Autophagy inhibition in combination cancer treatment","volume":"10","author":"Livesey K. 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