کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5859254 | 1132459 | 2013 | 6 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Organic cation transporter 1 mediates the uptake of monocrotaline and plays an important role in its hepatotoxicity
ترجمه فارسی عنوان
حمل کننده کاتیونی 1 از جذب تک سدیم جلوگیری می کند و نقش مهمی در سمیت کبد دارد
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کلمات کلیدی
SDSASP+OCT1MDCKDehydromonocrotaline1-methyl-4-phenylpyridiniumHBSSmonocrotalineMCTDHMCyP2-(N-morpholino)ethanesulfonic acid - 2- (N-مورفولینو) اتان سولفونیک اسیدDMSO - DMSOMPP+ - MPP +pyrrolizidine alkaloids - آلکالوئیدهای پیررولیزیدینTetraethylammonium - تترا اتیل آمونیومUptake - جذبorganic cation transporter 1 - حمل کننده کاتیونی آلی 1Dimethyl sulfoxide - دیمتیل سولفواکسیدsodium dodecyl sulfonate - سدیم دودسیل سولفوناتHepatotoxicity - سمیت کبدCytochrome P450 - سیتوکروم پی۴۵۰Hank's balanced salt solution - محلول نمک متعادل هانکMeS - مسPAS - نهTEA - چایLiver - کبدMadin–Darby Canine Kidney - کلیه کلیوی کلیوی Madin-Darby
موضوعات مرتبط
علوم زیستی و بیوفناوری
علوم محیط زیست
بهداشت، سم شناسی و جهش زایی
چکیده انگلیسی
Monocrotaline (MCT) is a kind of toxic retronecine-type pyrrolizidine alkaloids (PAs) from plants of Crotalaria, which can be bio-activated by cytochrome P450 (CYP) enzymes in liver and then induce hepatotoxicity. Since CYPs are localized in the endoplasmic reticulum, the influx of MCT to the liver is the key step for its hepatotoxicity. The objective of the present study was to investigate the role of organic cation transporter 1 (OCT1), a transporter mainly expressed in liver, in the uptake of MCT and in hepatotoxicity induced by MCT. The results revealed that MCT markedly inhibited the uptake of 1-methyl-4-phenylpyridinium (MPP+), an OCT1 substrate, in Madin-Darby canine kidney (MDCK) cells stably expressing human OCT1 (MDCK-hOCT1) with the IC50 of 5.52 ± 0.56 μM. The uptake of MCT was significantly higher in MDCK-hOCT1 cells than in MDCK-mock cells, and MCT uptake in MDCK-hOCT1 cells followed Michaelis-Menten kinetics with the Km and Vmax values of 25.0 ± 6.7 μM and 266 ± 64 pmol/mg protein/min, respectively. Moreover, the OCT1 inhibitors, such as quinidine, d-tetrahydropalmatine (d-THP), obviously inhibited the uptake of MCT in MDCK-hOCT1 cells and isolated rat primary hepatocytes, and attenuated the viability reduction and LDH release of the primary cultured rat hepatocytes caused by MCT. In conclusion, OCT1 mediates the hepatic uptake of MCT and may play an important role in MCT induced-hepatotoxicity.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology - Volume 311, Issue 3, 15 September 2013, Pages 225-230
Journal: Toxicology - Volume 311, Issue 3, 15 September 2013, Pages 225-230
نویسندگان
Meijuan Tu, Siyuan Sun, Kai Wang, Xueying Peng, Ruihan Wang, Liping Li, Su Zeng, Hui Zhou, Huidi Jiang,