کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5823632 | 1118344 | 2013 | 45 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Drug metabolizing enzyme and transporter protein profiles of hepatocytes derived from human embryonic and induced pluripotent stem cells
ترجمه فارسی عنوان
پروتئین آنزیم و پروتئین متابولیسم مواد مخدر متشکل از سلول های بنیادی پلوروپتوژن جنینی و القا شده بدن انسان
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کلمات کلیدی
BcrphiPSCOCT1OATP1B1NtcpMDR1BSEPE3SMrp2BSPTCACyPHepatocytes - hepatocyteshESC - hescestrone-3-sulfate - استرون -3 سولفاتTaurocholic acid - اسید تاورچولیکorganic cation transporter 1 - حمل کننده کاتیونی آلی 1Ritonavir - ریتونویرHuman induced pluripotent stem cells - سلول های بنیادی تکامل یافته القا شده توسط انسانhuman embryonic stem cells - سلول های بنیادی جنینی انسانRIT - سوار شدنCytochrome P450 - سیتوکروم پی۴۵۰transporter proteins - پروتئین حمل کنندهbreast cancer resistance protein - پروتئین مقاومت به سرطان سینهmultidrug resistance protein 1 - پروتئین مقاومتی چند دارویی 1Multidrug resistance protein 2 - پروتئین مقاومتی چند دارویی 2Bile salt export pump - پمپ صادرات نمک صفر
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
داروشناسی
چکیده انگلیسی
Human embryonic and induced pluripotent stem cell-derived hepatocytes (hESC-Hep and hiPSC-Hep) have the potential to provide relevant human in vitro model systems for toxicity testing and drug discovery studies. In this study, the expression and function of important drug metabolizing cytochrome P450 (CYP) enzymes and transporter proteins in hESC-Hep and hiPSC-Hep were compared to cryopreserved human primary hepatocytes (hphep) and HepG2 cells. Overall, CYP activities in hESC-Hep and hiPSC-Hep were much lower than in hphep cultured for 4Â h, but CYP1A and 3A activities were comparable to levels in hphep cultured for 48Â h (CYP1A: 35% and 26% of 48Â h hphep, respectively; CYP3A: 80% and 440% of 48Â h hphep, respectively). Importantly, in hESC-Hep and hiPSC-Hep, CYP activities were stable or increasing for at least one week in culture which was in contrast to the rapid loss of CYP activities in cultured hphep between 4 and 48Â h after plating. With regard to transporters, in hESC-Hep and hiPSC-Hep, pronounced NTCP activity (17% and 29% of 4Â h hphep, respectively) and moderate BSEP activity (6% and 8% of 4Â h hphep, respectively) were observed. Analyses of mRNA expression and immunocytochemistry supported the observed CYP and transporter activities and showed expression of additional CYPs and transporters. In conclusion, the stable expression and function of CYPs and transporters in hESC-Hep and hiPSC-Hep for at least one week opens up the possibility to reproducibly perform long term and extensive studies, e.g. chronic toxicity testing, in a stem cell-derived hepatic system.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical Pharmacology - Volume 86, Issue 5, 1 September 2013, Pages 691-702
Journal: Biochemical Pharmacology - Volume 86, Issue 5, 1 September 2013, Pages 691-702
نویسندگان
Maria Ulvestad, Pär Nordell, Annika Asplund, Marie Rehnström, Susanna Jacobsson, Gustav Holmgren, Lindsay Davidson, Gabriella Brolén, Josefina Edsbagge, Petter Björquist, Barbara Küppers-Munther, Tommy B. Andersson,