Schisandrin B enhances the glutathione redox cycling and protects against oxidant injury in different types of cultured cells.
Tert-butylhydroperoxide (tBHP) challenge caused an initial depletion of cellular reduced glutathione (GSH), which was followed by a gradual restoration of cellular GSH in AML12, H9c2, and differentiated PC12 cells. The time-dependent changes in cellular GSH induced by tBHP were monitored as a measure of GSH recovery capacity (GRC), of which glutathione reductase (GR)-mediated glutathione redox cycling and γ-glutamate cysteine ligase (GCL)-mediated GSH synthesis were found to play an essential role. While glutathione redox cycling sustained the GSH level during the initial tBHP-induced depletion, GSH synthesis restores the GSH level thereafter. The effects of (-)schisandrin B [(-)Sch B] and its analogs (Sch A and Sch C) on GRC were also examined in the cells. (-)Sch B and Sch C, but not Sch A, ameliorated the extent of tBHP-induced GSH depletion, indicative of enhanced glutathione redox cycling. However, the degree of restoration of GSH post-tBHP challenge was not affected or even decreased. Pretreatment with (-)Sch B and Sch C, but not Sch A, protected against oxidant injury in the cells. The (-)Sch B afforded cytoprotection was abolished by N,N'-bis(chloroethyl)-N-nitrosourea pretreatment suggesting the enhancement of glutathione redox cycling is crucially involved in the cytoprotection afforded by (-)Sch B against oxidative stress-induced cell injury.
Division of Life Science, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong SAR, China.
Philip Y
PY
Lam
Pou Kuan
PK
Leong
Na
N
Chen
Kam Ming
KM
Ko
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002330:Carmustine / Q000494:pharmacology; D002460:Cell Line; D034242:Cyclooctanes / Q000494:pharmacology; D019610:Cytoprotection; D005452:Fluoresceins; D005978:Glutathione / Q000378:metabolism*; D005980:Glutathione Reductase / Q000037:antagonists & inhibitors / Q000378:metabolism; D017705:Lignans / Q000494:pharmacology*; D051379:Mice; D010042:Ouabain / Q000031:analogs & derivatives; D016877:Oxidants; D018384:Oxidative Stress; D011083:Polycyclic Compounds / Q000494:pharmacology*; D051381:Rats; D020122:tert-Butylhydroperoxide
D000975:Antioxidants; D034242:Cyclooctanes; D005452:Fluoresceins; D017705:Lignans; D016877:Oxidants; D011083:Polycyclic Compounds; C109049:rhodol green-ethylenediamine-ouabain; C015499:schizandrin B; D010042:Ouabain; C034734:schizandrin A; D020122:tert-Butylhydroperoxide; C031409:schizandrin C; D005980:Glutathione Reductase; D005978:Glutathione; D002330:Carmustine