Schisandrin B induced antioxidant response is partly mediated by cytochrome P-4502E1 catalyzed reaction in mouse liver.
In order to explore the role of cytochrome P-450 (CYP) 2E1 in schisandrin B (Sch B)-induced antioxidant and heat shock responses, the effects of Sch B treatment on hepatic mitochondrial glutathione antioxidant status (mtGAS) and heat shock protein (Hsp)25/70 expression were compared between wild-type and cyp2e1 knock-out C57B/6N mice. Cyp2e1 knock-out mice exhibited a significantly smaller degree of Sch B-induced enhancement in hepatic mtGAS when compared with the wild-type counterpart. But Hsp25/70 expression induced by Sch B was not affected. Sch B-induced enhancement of mtGAS was corroborated by the increase in hepatic mitochondrial antioxidant capacity, as assessed by in vitro measurement of oxidant production, with the enhancing effect being slightly reduced in the knock-out mice. Using liver microsomes prepared from wild-type and knock-out mice as a source of CYP, Sch B was found to be a good co-substrate for the CYP-catalyzed reaction, with the rate of NADPH oxidation observable in microsomes prepared from knock-out mice being slower. The CYP-catalyzed reaction with Sch B was associated with a concomitant production of oxidant species, with the extent of oxidant production being reduced in cyp2e1 knock-out mouse microsomes. Taken together, the results indicate that CYP2E1 is partly responsible for the hepatic metabolism of Sch B that may trigger the antioxidant response in vivo.
Chiu
Po Yee
PY
Department of Biochemistry, The Hong Kong University of Science & Technology, Clear Water Bay, Hong Kong, China.
Leung
Hoi Yan
HY
Poon
Michel K T
MK
Lee
Susanna S T
SS
Ko
Kam Ming
KM
D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology*; D002384:Catalysis / Q000187:drug effects; D034242:Cyclooctanes / Q000494:pharmacology; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005978:Glutathione / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism; D017705:Lignans / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D008930:Mitochondria, Liver / Q000187:drug effects / Q000201:enzymology*; D018832:Molecular Chaperones; D009249:NADP / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism; D011083:Polycyclic Compounds / Q000494:pharmacology*
D000975:Antioxidants; D034242:Cyclooctanes; D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins; C486113:Hsbp1 protein, mouse; D017705:Lignans; D018832:Molecular Chaperones; D009363:Neoplasm Proteins; D011083:Polycyclic Compounds; C015499:schizandrin B; D009249:NADP; D019392:Cytochrome P-450 CYP2E1; D005978:Glutathione