Premium
(−)Schisandrin B ameliorates paraquat‐induced oxidative stress by suppressing glutathione depletion and enhancing glutathione recovery in differentiated PC12 cells
Author(s) -
Lam Philip Y.,
Ming Ko Kam
Publication year - 2011
Publication title -
biofactors
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.204
H-Index - 94
eISSN - 1872-8081
pISSN - 0951-6433
DOI - 10.1002/biof.136
Subject(s) - glutathione , oxidative stress , paraquat , cytoprotection , chemistry , pharmacology , reactive oxygen species , lactate dehydrogenase , biochemistry , glutathione reductase , programmed cell death , apoptosis , glutathione peroxidase , biology , enzyme
Exposure to paraquat (PQ; N , N ′‐dimethyl‐4‐4′‐bipyridium), 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 (−)schisandrin B [(−)Sch B, a potent enantiomer of schisandrin B] on PQ‐induced 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 (−)Sch B (5 μM) protected against PQ‐induced toxicity in PC12 cells, as evidenced by the significant decrease in LDH leakage. (−)Sch B induced the cytochrome P ‐450‐mediated reactive oxygen species generation in differentiated PC12 cells. The cytoprotection afforded by (−)Sch B pretreatment was associated with an increase in cellular reduced glutathione (GSH) level as well as the enhancement of γ‐glutamylcysteine ligase (GCL) and glutathione reductase (GR) activity in PQ‐challenged cells. Both GCL and GR inhibitors abrogated the cytoprotective effect of (−)Sch B in PQ‐challenged cells. The biochemical mechanism underlying the GSH‐enhancing effect of (−)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‐catalyzed regeneration of GSH in (−)Sch B‐pretreated cells, the later enhanced GSH recovery was mainly mediated by GCL‐catalyzed GSH synthesis. The results suggest that (−)Sch B treatment may increase the resistance of dopaminergic cells against PQ‐induced oxidative stress through reducing the extent of oxidant‐induced GSH depletion and enhancing the subsequent GSH recovery.