کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2484367 | 1114308 | 2016 | 11 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Localization of Xenobiotic Transporter OCTN1/SLC22A4 in Hepatic Stellate Cells and Its Protective Role in Liver Fibrosis
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کلمات کلیدی
SLCcontrol siRNATNForganic cation transporters (OCT)OCTN14HNEdimethylnitrosamineConAHSCsNPCTGFDMNECMHFDFBSConcanavalin Aα-SMA4-hydroxy-2-nonenal - 4-هیدروکسی-2 غیرنالLC-MS/MS - LC-MS / MSNOx - NOXAntioxidants - آنتی اکسیدانAlpha-smooth muscle actin - آکتا عضله آلفا صافErgothioneine - ارگوتیزیونnonalcoholic steatohepatitis - استاتو هپاتیت غیر الکلیInduction - القاءNADPH oxidase - اکسیداز NADPH ErGO - بنابر اینtransforming growth factor - تبدیل فاکتور رشدsolute carrier - حامل رقیبTransporters - حمل و نقلMembrane transporter - حمل کننده غشاییhigh-fat diet - رژیم غذایی با چربی بالاfetal bovine serum - سرم جنین گاوNonparenchymal cells - سلول های غیر پارنشیمیHepatic stellate cells - سلولهای ستارهای کبدیLiquid chromatography-tandem mass spectrometry - طیف سنجی جرمی کروماتوگرافی مایع دو طرفهExtracellular matrix - ماتریکس خارج سلولیNash - نوش
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
اکتشاف دارویی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Xenobiotic transporters play key roles in disposition of certain therapeutic agents, although limited information is available on their roles other than pharmacokinetic issues. Here, suppressive effect of multispecific organic cation transporter OCTN1/SLC22A4 on liver fibrosis was proposed in liver injury models. After injection of hepatotoxins such as dimethylnitrosamine (DMN) or concanavalin A, hepatic fibrosis, and oxidative stress, evaluated in terms of Sirius red and 4-hydroxy-2-nonenal staining, respectively, were more severe in liver of octn1/slc22a4 gene knockout (octn1â/â) mice than that in wild-type mice. DMN treatment markedly increased α-smooth muscle actin and F4/80, markers of activated stellate and Kupffer cells, respectively, in liver of octn1â/â, but had less effect in wild-type mice. Thus, octn1/slc22a4 gene deletion results in more severe hepatic fibrosis, oxidative stress, and inflammation. DMN-treated wild-type mice showed increased Octn1 staining and hepatic concentration of its food-derived antioxidant ergothioneine (ERGO). The upregulated Octn1 was co-localized with α-smooth muscle actin. Functional expression of Octn1 was demonstrated in activated human hepatic stellate cell lines, LI90 and LX-2. Provision of ERGO-rich feed ameliorated DMN-induced liver fibrosis and oxidative stress. Overall, Octn1 is upregulated in activated stellate cells, resulting in increased delivery of its substrate antioxidant ERGO and a protective effect against liver fibrosis.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 105, Issue 5, May 2016, Pages 1779-1789
Journal: Journal of Pharmaceutical Sciences - Volume 105, Issue 5, May 2016, Pages 1779-1789
نویسندگان
Yaliang Tang, Yusuke Masuo, Yoshio Sakai, Tomohiko Wakayama, Tomoko Sugiura, Ryuichi Harada, Azusa Futatsugi, Takuya Komura, Noritaka Nakamichi, Hirotaka Sekiguchi, Keita Sutoh, Koji Usumi, Shoichi Iseki, Shuichi Kaneko, Yukio Kato,