{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T04:03:53Z","timestamp":1791518633912,"version":"4.3.4"},"reference-count":42,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2017,12,5]],"date-time":"2017-12-05T00:00:00Z","timestamp":1512432000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81402481"],"award-info":[{"award-number":["81402481"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2018,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>\n                      Glutathione (\n                      <jats:styled-content style=\"fixed-case\">GSH<\/jats:styled-content>\n                      ) and\n                      <jats:styled-content style=\"fixed-case\">GSH<\/jats:styled-content>\n                      \u2010related enzymes constitute the most important defense system that protects cells from free radical, radiotherapy, and chemotherapy attacks. In this study, we aim to explore the potential role and regulatory mechanism of the\n                      <jats:styled-content style=\"fixed-case\">GSH<\/jats:styled-content>\n                      redox cycle in drug resistance in glioblastoma multiforme (\n                      <jats:styled-content style=\"fixed-case\">GBM<\/jats:styled-content>\n                      ) cells. We found that temozolomide (\n                      <jats:styled-content style=\"fixed-case\">TMZ<\/jats:styled-content>\n                      )\u2010resistant glioma cells displayed lower levels of endogenous reactive oxygen species and higher levels of total antioxidant capacity and\n                      <jats:styled-content style=\"fixed-case\">GSH<\/jats:styled-content>\n                      than sensitive cells. Moreover, the expression of glutathione reductase (\n                      <jats:styled-content style=\"fixed-case\">GSR<\/jats:styled-content>\n                      ), the key enzyme of the\n                      <jats:styled-content style=\"fixed-case\">GSH<\/jats:styled-content>\n                      redox cycle, was higher in\n                      <jats:styled-content style=\"fixed-case\">TMZ<\/jats:styled-content>\n                      \u2010resistant cells than in sensitive cells. Furthermore, silencing\n                      <jats:styled-content style=\"fixed-case\">GSR<\/jats:styled-content>\n                      in drug\u2010resistant cells improved the sensitivity of cells to\n                      <jats:styled-content style=\"fixed-case\">TMZ<\/jats:styled-content>\n                      or cisplatin. Conversely, the over\u2010expression of\n                      <jats:styled-content style=\"fixed-case\">GSR<\/jats:styled-content>\n                      in sensitive cells resulted in resistance to chemotherapy. In addition, the\n                      <jats:styled-content style=\"fixed-case\">GSR<\/jats:styled-content>\n                      enzyme partially prevented the oxidative stress caused by pro\u2010oxidant L\u2010buthionine \u2010sulfoximine. The modulation of redox state by\n                      <jats:styled-content style=\"fixed-case\">GSH<\/jats:styled-content>\n                      or L\u2010buthionine \u2013sulfoximine regulated\n                      <jats:styled-content style=\"fixed-case\">GSR<\/jats:styled-content>\n                      \u2010mediated drug resistance, suggesting that the action of\n                      <jats:styled-content style=\"fixed-case\">GSR<\/jats:styled-content>\n                      in drug resistance is associated with the modulation of redox homeostasis. Intriguingly, a trend toward shorter progress\u2010free survival was observed among\n                      <jats:styled-content style=\"fixed-case\">GBM<\/jats:styled-content>\n                      patients with high\n                      <jats:styled-content style=\"fixed-case\">GSR<\/jats:styled-content>\n                      expression. These results indicated that\n                      <jats:styled-content style=\"fixed-case\">GSR<\/jats:styled-content>\n                      is involved in mediating drug resistance and is a potential target for improving\n                      <jats:styled-content style=\"fixed-case\">GBM<\/jats:styled-content>\n                      treatment.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>\n                      <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                        <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc14250-fig-0009-m.png\">\n                          <jats:alt-text>image<\/jats:alt-text>\n                        <\/jats:graphic>\n                      <\/jats:boxed-text>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jnc.14250","type":"journal-article","created":{"date-parts":[[2017,11,3]],"date-time":"2017-11-03T12:49:52Z","timestamp":1509713392000},"page":"93-104","source":"Crossref","is-referenced-by-count":160,"title":["Glutathione reductase mediates drug resistance in glioblastoma cells by regulating redox homeostasis"],"prefix":"10.1111","volume":"144","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8465-1414","authenticated-orcid":false,"given":"Zhongling","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacology Tianjin Medical University Cancer Institute and Hospital National Clinical Research Center for Cancer Key Laboratory of Cancer Prevention and Therapy Tianjin's Clinical Research Center for Cancer Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuangshuang","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology Tianjin Medical University Cancer Institute and Hospital National Clinical Research Center for Cancer Key Laboratory of Cancer Prevention and Therapy Tianjin's Clinical Research Center for Cancer Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yibo","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology Tianjin Medical University Cancer Institute and Hospital National Clinical Research Center for Cancer Key Laboratory of Cancer Prevention and Therapy Tianjin's Clinical Research Center for Cancer Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Ren","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology Tianjin Medical University Cancer Institute and Hospital National Clinical Research Center for Cancer Key Laboratory of Cancer Prevention and Therapy Tianjin's Clinical Research Center for Cancer Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoguang","family":"Ying","sequence":"additional","affiliation":[{"name":"Department of Tumor Cell Biology Tianjin Medical University Cancer Institute and Hospital Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3691-9823","authenticated-orcid":false,"given":"Zhao","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology Tianjin Medical University Cancer Institute and Hospital National Clinical Research Center for Cancer Key Laboratory of Cancer Prevention and Therapy Tianjin's Clinical Research Center for Cancer Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,12,5]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2011.11.016"},{"key":"e_1_2_7_3_1","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1007\/978-94-007-7217-5_24","volume-title":"Tumors of the Central Nervous System","author":"Backos D. 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