Schisandrin B induced antioxidant response is partly mediated by cytochrome P-4502E1 catalyzed reaction in mouse liver

Molecular and Cellular Biochemistry - Tập 293 - Trang 87-92 - 2006
Po Yee Chiu1, Hoi Yan Leung1, Michel K. T. Poon1, Susanna S. T. Lee2, Kam Ming Ko1
1Department of Biochemistry, The Hong Kong University of Science & Technology, China
2Department of Biochemistry, The Chinese University of Hong Kong, China

Tóm tắt

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.

Tài liệu tham khảo

Hancke JL, Burgos RA, Ahumada F: Schisandra chinensis (Turcz.) Baill. Fitoterapia 70: 451–471, 1999 Ip SP, Poon MKT, Wu SS, Che CT, Ng KH, Kong YC, Ko KM: Effect of schisandrin B on hepatic glutathione antioxidant system in mice: protection against carbon tetrachloride toxicity. Planta Med 61: 398–401, 1995 Ko KM, Yiu HY: Schisandrin B modulates the ischemia-reperfusion induced changes in non-enzymatic antioxidant levels in isolated-perfused rat hearts. Mol Cell Biochem 220: 141–147, 2001 Ip SP, Ko KM: The crucial antioxidant action of schisandrin B in protecting against carbon tetrachloride hepatotoxicity in mice: a comparative study with butylated hydroxytoluene. Biochem Pharmacol 52: 1687–1693, 1996 Chiu PY, Ko KM: Time-dependent enhancement in mitochondrial glutathione status and ATP generation capacity by schisandrin B treatment decreases the susceptibility of rat hearts to ischemia-reperfusion injury. Biofactors 19: 43–51, 2003 Chiu PY, Tang MH, Mak DH, Poon MKT, Ko KM: Hepatoprotective mechanism of schisandrin B: role of mitochondrial glutathione antioxidant status and heat shock proteins. Free Radic Biol Med 35: 368–380, 2003 Chiu PY, Mak DHF, Poon MKT, Ko KM: Role of cytochrome P-450 in schisandrin B-induced antioxidant and heat shock responses in mouse liver. Life Sci 77: 2887–2895, 2005 Gonzalez FJ: The molecular biology of cytochrome P450s. Pharmacol Rev 40: 243–288, 1988 Guengerich FP, Kim DH, Iwasaki M: Role of human cytochrome P-450 IIE1 in the oxidation of many low molecular weight cancer suspects. Chem Res Toxicol 4: 168–179, 1991 Ortiz de Montellano PR, Mathews JM: Autocatalytic alkylation of the cytochrome P-450 prosthetic haem group by 1-aminobenzotriazole. Isolation of an NN-bridged benzyne-protoporphyrin IX adduct. Biochem J 195: 761–764, 1981 Evans WH: Isolation and characterization of membranes and cell organelles. In: Rickwood D (ed). Preparative Centrifugation: A Practical Approach, Oxford University Press: New York, 1992, pp 233–270 Griffith OW: Determination of glutathione and glutathione disulfide using glutathione reductase and 2-vinylpyridine. Anal Biochem 106: 207–212, 1980 Chiu PY, Mak DH, Poon MKT, Ko KM: In vivo antioxidant action of a lignan-enriched extract of Schisandra fruit and an anthraquinone-containing extract of Polygonum root in comparison with schisandrin B and emodin. Planta Med 68: 951–956, 2002 Ip SP, Che CT, Kong YC, Ko KM: Effects of schisandrin B pretreatment on tumor necrosis factor-alpha induced apoptosis and Hsp70 expression in mouse liver. Cell Stress Chaperones 6: 44–48, 2001 Wong FW, Chan WY, Lee SS: Resistance to carbon tetrachloride-induced hepatotoxicity in mice which lack CYP2E1 expression. Toxicol Appl Pharmacol 153: 109–118, 1998 Lee SS, Buters JT, Pineau T, Fernandez-Salguero P, Gonzalez FJ: Role of CYP2E1 in the hepatotoxicity of acetaminophen. J Biol Chem 271: 12063–12067, 1996 Omiecinski CJ, Remmel RP, Hosagrahara VP: Concise review of the cytochrome P450s and their roles in toxicology. Toxicol Sci 48: 151–156, 1999 Lieber CS: Cytochrome P-4502E1: its physiological and pathological role. Physiol Rev 77: 517–44. Owuor, ED, Kong AN: Antioxidants and oxidants regulated signal transduction pathways. Biochem Pharmacol 64: 765–770, 1997 Paroo Z, Meredith MJ, Locke M, Haist JV, Karmazyn M, Noble EG: Redox signaling of cardiac HSF1 DNA binding. Am J Physiol Cell Physiol 283: C404–C411, 2002 Ip SP, Yiu HY, Ko KM: Differential effect of schisandrin B and dimethyl diphenyl bicarboxylate (DDB) on hepatic mitochondrial glutathione redox status in carbon tetrachloride intoxicated mice. Mol Cell Biochem 205: 111–4, 2000