{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T22:31:42Z","timestamp":1789079502174,"version":"build-2803163510"},"reference-count":35,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2011,1,13]],"date-time":"2011-01-13T00:00:00Z","timestamp":1294876800000},"content-version":"vor","delay-in-days":12,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["BioFactors"],"published-print":{"date-parts":[[2011,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Exposure to paraquat (PQ;<jats:italic>N<\/jats:italic>,<jats:italic>N<\/jats:italic>\u2032\u2010dimethyl\u20104\u20104\u2032\u2010bipyridium), a potent herbicide, can lead to neuronal cell death and increased risk of Parkinson's disease because of oxidative stress. In this study, we investigated the effect of (\u2212)schisandrin B [(\u2212)Sch B, a potent enantiomer of schisandrin B] on PQ\u2010induced cell injury in differentiated pheochromocytoma cells (PC12). PQ treatment caused cell injury in PC12 cells, as indicated by the significant increase in lactate dehydrogenase (LDH) leakage. Pretreatment with (\u2212)Sch B (5 \u03bcM) protected against PQ\u2010induced toxicity in PC12 cells, as evidenced by the significant decrease in LDH leakage. (\u2212)Sch B induced the cytochrome<jats:italic>P<\/jats:italic>\u2010450\u2010mediated reactive oxygen species generation in differentiated PC12 cells. The cytoprotection afforded by (\u2212)Sch B pretreatment was associated with an increase in cellular reduced glutathione (GSH) level as well as the enhancement of \u03b3\u2010glutamylcysteine ligase (GCL) and glutathione reductase (GR) activity in PQ\u2010challenged cells. Both GCL and GR inhibitors abrogated the cytoprotective effect of (\u2212)Sch B in PQ\u2010challenged cells. The biochemical mechanism underlying the GSH\u2010enhancing effect of (\u2212)Sch B was further investigated in PC12 cells subjected to an acute peroxide challenge. Although the initial GSH depletion induced by peroxide was reduced through GR\u2010catalyzed regeneration of GSH in (\u2212)Sch B\u2010pretreated cells, the later enhanced GSH recovery was mainly mediated by GCL\u2010catalyzed GSH synthesis. The results suggest that (\u2212)Sch B treatment may increase the resistance of dopaminergic cells against PQ\u2010induced oxidative stress through reducing the extent of oxidant\u2010induced GSH depletion and enhancing the subsequent GSH recovery.<\/jats:p>","DOI":"10.1002\/biof.136","type":"journal-article","created":{"date-parts":[[2011,1,13]],"date-time":"2011-01-13T19:26:04Z","timestamp":1294946764000},"page":"51-57","source":"Crossref","is-referenced-by-count":20,"title":["(\u2212)Schisandrin B ameliorates paraquat\u2010induced oxidative stress by suppressing glutathione depletion and enhancing glutathione recovery in differentiated PC12 cells"],"prefix":"10.1002","volume":"37","author":[{"given":"Philip Y.","family":"Lam","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kam","family":"Ming Ko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2011,1,13]]},"reference":[{"key":"e_1_2_5_2_2","doi-asserted-by":"publisher","DOI":"10.1177\/096032718800700103"},{"key":"e_1_2_5_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2559.1980.tb02911.x"},{"key":"e_1_2_5_4_2","first-page":"243","article-title":"Brain damage due to paraquat poisoning: a fatal case with neuropathological examination of the brain","volume":"9","author":"Hughes J. 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