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571.
Kathryn B. Garber 《American journal of human genetics》2016,99(5):1003-1004
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Datta G Garber DW Chung BH Chaddha M Dashti N Bradley WA Gianturco SH Anantharamaiah GM 《Journal of lipid research》2001,42(6):959-966
We previously showed 1 that a peptide, Ac-hE18A-NH(2), in which the arginine-rich heparin-binding domain of apolipoprotein E (apoE) [residues 141;-150] (LRKLRKRLLR), covalently linked to 18A (DWLKAFYDKVAEKLKEAF; a class A amphipathic helix with high lipid affinity), enhanced LDL uptake and clearance. Because VLDL and remnants contain more cholesterol per particle than LDL, enhanced hepatic clearance of VLDL could lead to an effective lowering of plasma cholesterol. Therefore, in the present article we compared the ability of this peptide to mediate/facilitate the uptake and degradation of LDL and VLDL in HepG2 cells. The peptide Ac-hE18A-NH(2), but not Ac-18A-NH(2), enhanced the uptake of LDL by HepG2 cells 5-fold and its degradation 2-fold. The association of the peptides with VLDL resulted in the displacement of native apoE; however, only Ac-hE18A-NH(2) but not Ac-18A-NH(2) caused markedly enhanced uptake (6-fold) and degradation (3-fold) of VLDL. Ac-hE18A-NH(2) also enhanced the uptake (15-fold) and degradation (2-fold) of trypsinized VLDL Sf 100;-400 (containing no immuno-detectable apoE), indicating that the peptide restored the cellular interaction of VLDL in the absence of its essential native ligand (apoE). Pretreatment of HepG2s with heparinase and heparitinase abrogated all peptide-mediated enhanced cellular activity, implicating a role for cell-surface heparan sulfate proteoglycans (HSPG). Intravenous administration of Ac-hE18A-NH(2) into apoE gene knockout mice reduced plasma cholesterol by 88% at 6 h and 30% at 24 h after injection. We conclude that this dual-domain peptide associates with LDL and VLDL and results in rapid hepatic uptake via a HSPG-facilitated pathway. 相似文献
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Kathryn?B. Garber 《American journal of human genetics》2013,93(5):777-778
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Kathryn?B. Garber 《American journal of human genetics》2013,93(4):589-590
578.
Kathryn?B. Garber 《American journal of human genetics》2013,92(3):315-316
579.
Adaptive evolution of G-protein coupled receptor genes 总被引:2,自引:0,他引:2
The phylogeny and patterns of nucleotide substitutions in the visual
pigment genes, adrenergic receptor genes, muscarinic receptor genes, and in
the human mas oncogene were studied by comparing their DNA sequences. The
evolutionary tree obtained shows that the visual pigment genes and mas
oncogene form one cluster and that the receptor genes form another. In the
evolution of rhodopsin genes, synonymous substitutions outnumber
nonsynonymous substitutions. This is consistent with the neutral theory of
molecular evolution. However, the early evolutionary stages of alpha- and
beta-adrenergic and muscarinic receptors are notable for significantly more
nonsynonymous substitutions than synonymous substitutions, suggesting the
acquisition of novel functional adaptations. Variable rates of
nonsynonymous changes in different domains of these proteins reveal DNA
segments that might have been important in their functional adaptations.
相似文献
580.
Kathryn B. Garber 《American journal of human genetics》2012,90(2):173-174