کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5823841 | 1118367 | 2012 | 8 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Pharmacodynamic and pharmacokinetic analysis of apoE4 [L261A, W264A, F265A, L268A, V269A], a recombinant apolipoprotein E variant with improved biological properties
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کلمات کلیدی
APOE2APOE4Apolipoprotein E2PAGEApoA-IApolipoprotein E3LRP-1GFPHDLVLDLApolipoproteins ESDSApoE3ApoE−/− - ApoE - / -LDL-receptor - LDL گیرندهAdenovirus - آدنوویروسApoe - آپوApolipoprotein A-I - آپولیپوپروتئین A-Iapolipoprotein E - آپولیپوپروتئین Eapolipoprotein E4 - آپولیپوپروتئین E4polyacrylamide gel electrophoresis - الکتروفورز ژل پلی آکریل آمیدELISA - تست الیزاsodium dodecyl sulfate - سدیم دودسیل سولفاتPharmacodynamics - فارماکودینامیکPharmacokinetics - فارماکوکینتیکhigh density lipoprotein - لیپوپروتئین با چگالی بالاvery low density lipoprotein - لیپوپروتئین چگالی بسیار کم استwild-type - نوع وحشیHypercholesterolemia - هیپرکلسترولمی polymerase chain reaction - واکنش زنجیره ای پلیمرازPCR - واکنش زنجیرهٔ پلیمرازGreen fluorescence protein - پروتئین فلورسانس سبز
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
داروشناسی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Pharmacodynamic and pharmacokinetic analysis of apoE4 [L261A, W264A, F265A, L268A, V269A], a recombinant apolipoprotein E variant with improved biological properties Pharmacodynamic and pharmacokinetic analysis of apoE4 [L261A, W264A, F265A, L268A, V269A], a recombinant apolipoprotein E variant with improved biological properties](/preview/png/5823841.png)
چکیده انگلیسی
Physiological levels of wild-type (wt) apolipoprotein E (apoE) in plasma mediate the clearance of cholesterol-rich atherogenic lipoprotein remnants while higher than normal plasma apoE concentrations fail to do so and trigger hypertriglyceridemia. This property of wt apoE reduces significantly its therapeutic value as a lead biological for the treatment of dyslipidemia. Recently, we reported the generation of a recombinant apoE variant, apoE4 [L261A, W264A, F265A, L268A, V269A] (apoE4mut1) with improved biological functions. Specifically, in apoE-deficient (apoEâ/â) mice this variant can normalize high plasma cholesterol levels without triggering hypertriglyceridemia, even at supraphysiological levels of expression. In the present study we performed pharmacodynamic and pharmacokinetic analysis of apoE4mut1 in experimental mice. Using adenovirus-mediated gene transfer in LDL receptor deficient (LDLrâ/â) mice, we show that the cholesterol lowering potential of apoE4mut1 is dependent on the expression of a functional classical LDLr. Bolus infusion of apoE4mut1-containing proteoliposomes in apoEâ/â mice fed western-type diet for 6 weeks indicated that exogenously synthesized apoE4mut1 maintains intact its ability to normalize the high cholesterol levels of these mice with a maximum pharmacological effect obtained at 10Â h post-treatment. Interestingly, plasma cholesterol levels remained significantly reduced up to 24Â h following intravenous administration of apoE4mut1 proteoliposomes. Measurements of plasma apoE levels indicated that apoE4mut1 in the form of proteoliposomes used in the study has a half-life of 15.8Â h. Our data suggest that purified apoE4mut1 may be an attractive new candidate for the acute correction of hypercholesterolemia in subjects expressing functional LDL receptor.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical Pharmacology - Volume 84, Issue 11, 1 December 2012, Pages 1451-1458
Journal: Biochemical Pharmacology - Volume 84, Issue 11, 1 December 2012, Pages 1451-1458
نویسندگان
Angeliki Lampropoulou, Vassilis I. Zannis, Kyriakos E. Kypreos,