کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5847972 | 1561615 | 2015 | 7 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Mechanism-based inactivation of cytochrome P450 2B6 by isoimperatorin
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کلمات کلیدی
GSHIsoimperatorinRLMsIDAEPIMRMCytochrome P450 2B6NADPHDMSO - DMSOLC–MS/MS - LC-MS / MSMS/MS - MS / MSenhanced product ion - افزایش یون محصولcollision energy - انرژی برخوردDimethyl sulfoxide - دیمتیل سولفواکسیدSOD - سدSuperoxide dismutase - سوکسوکس دیسموتازMass spectrometry - طیف سنجی جرمیTandem mass spectrometry - طیف سنجی جرمی پشت سر هم یا متوالیMechanism-based inactivator - غیر فعال کننده مکانیسمReactive metabolite - متابولیت واکنش پذیرRat liver microsomes - میکروسوم های کبدی موشMultiple-reaction monitoring - نظارت چند واکنشliquid chromatography - کروماتوگرافی مایعliquid chromatography coupled to tandem mass spectrometry - کروماتوگرافی مایع همراه با طیف سنجی جرمی دو طرفهInformation-Dependent Acquisition - کسب اطلاعات وابستهGlutathione - گلوتاتیون
موضوعات مرتبط
علوم زیستی و بیوفناوری
علوم محیط زیست
بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله

چکیده انگلیسی
Isoimperatorin (IIMP), a 6,7-furanocoumarin derivative, occurs in many common medicinal herbs. Human exposure to IIMP mainly results from intake of fruits, foods and medicinal herbs. We examined the irreversible inhibitory effect of IIMP on cytochrome P450 2B6. IIMP was found to cause time-dependent inhibition of CYP2B6. In addition, the loss of CYP2B6 activity occurred in a NAPDH- and concentration-dependent manner. About 60% of activity of CYP2B6 was suppressed after its incubation with IIMP at 25 μM for 9 min. Enzyme kinetic studies were performed, kinact for IIMP was found to be 0.071 minâ1, and KI was 17.1 μM, respectively. Glutathione and catalase/superoxide dismutase showed little protective effects on CYP2B6 against the inactivation by IIMP. S-Mephenytoin, a substrate of CYP2B6, mildly prevented the enzyme from the inactivation induced by IIMP. The estimated partition ratio of the inactivation was approximately 211. Additionally, a γ-ketoenal intermediate was identified in microsomal incubations with IIMP. CYPs 2B6, 2D6, and 1A2 were the major enzymes responsible for the metabolic activation of IIMP. In conclusion, IIMP is a mechanism-based inactivator of CYP2B6. The formation of γ-ketoenal intermediate may be responsible for the enzyme inactivation.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Chemico-Biological Interactions - Volume 226, 25 January 2015, Pages 23-29
Journal: Chemico-Biological Interactions - Volume 226, 25 January 2015, Pages 23-29
نویسندگان
Jiaojiao Cao, Liwei Zheng, Lin Ji, Dan Lu, Ying Peng, Jiang Zheng,