کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5860770 | 1133239 | 2011 | 8 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Lipopolysaccharide down-regulates carbolesterases 1 and 2 and reduces hydrolysis activity in vitro and in vivo via p38MAPK-NF-κB pathway
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کلمات کلیدی
NF-κB4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)-1H-imidazolehCE1dimethysulfoxideSB203580human pregnane X receptorDMEsPDTCCYP450PXRp38MAPKU0126hPXRqRT-PCRPBSLPSDMEMGAPDHDMSO - DMSOERK1/2 - ERK1 / 2Dulbecco's modified Eagle's medium - Medal of Eagle اصلاح شده DulbeccoAmmonium pyrrolidinedithiocarbamate - آمونیوم پیرولیدیدیتیو کرباماتtumor necrosis factor α - تومور نکروز عامل αnormal saline - سالین نرمالCytochrome P450 - سیتوکروم پی۴۵۰TNF-α - فاکتور نکروز توموری آلفاnuclear factor kappa B - فاکتور هسته ای کاپا Blipopolysaccharide - لیپوپلی ساکاریدPhosphate-buffered saline - محلول نمک فسفات با خاصیت بافریquantitative reverse transcription-polymerase chain reaction - واکنش زنجیره ای رونویسی معکوس و پلیمریزا معکوسpolymerase chain reaction - واکنش زنجیره ای پلیمرازPCR - واکنش زنجیرهٔ پلیمرازp38 mitogen-activated protein kinase - پروتئین کیناز متیوژن فعال p38glyceraldehyde-3-phosphate dehydrogenase - گلیسرالیدید-3-فسفات دهیدروژنازPregnane X receptor - گیرنده پیش گران X
موضوعات مرتبط
علوم زیستی و بیوفناوری
علوم محیط زیست
بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Carboxylesterases constitute a class of enzymes that hydrolyze drugs containing such functional groups as carboxylic acid ester, amide, and thioester. Hydrolysis of many drugs is reduced in liver diseases such as hepatitis and cirrhosis. In this study, we have demonstrated, in vitro and in vivo, treatment with LPS decreased the expression of HCE1 and HCE2 and the capacity of hydrolytic activity. In HepG2 cells, the decreased expression by LPS occurred at both mRNA and protein levels. Both HCE1 and HCE2 promoters were significantly repressed by LPS, and the repression was comparable with the decrease in HCE1 and HCE2 mRNA, suggesting the transrepression is responsible for suppressed expression. Further study showed that both PDTC, a NF-κB inhibitor, and SB203580, a p38MAPK inhibitor, could abolish the repression of HCE1 and HCE2 mediated by LPS, but U0126, a selective ERK1/2 inhibitor, could not do so, suggesting the repression of HCE1 and HCE2 by LPS through the p38MAPK-NF-κB pathway. In addition, being pretreated with LPS, HepG2 cells altered the cellular responsiveness to ester therapeutic agents, including clopidogrel (hydrolyzed by HCE1) and irinotecan (hydrolyzed by HCE2). The altered cellular responsiveness occurred at low micromolar concentrations, suggesting that suppressed expression of carboxylesterases by LPS has profound pharmacological and toxicological consequences, particularly with those that are hydrolyzed in an isoform-specific manner. This study provides new insight into the understanding of the pharmacological and toxicological effects and the mechanisms for repressing drug metabolism enzymes in inflammation.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology Letters - Volume 201, Issue 3, 25 March 2011, Pages 213-220
Journal: Toxicology Letters - Volume 201, Issue 3, 25 March 2011, Pages 213-220
نویسندگان
Zhao Mao, Yang Li, Yan Peng, Xiaofei Luan, Haiyan Gui, Xuemin Feng, Gang Hu, Jianping Shen, Bingfang Yan, Jian Yang,