Abstract：
:Hepatic very-low-density lipoprotein particles (VLDL) containing full-length apolipoprotein B100 are metabolized in the blood stream to low-density lipoprotein (LDL) particles, whose elevated levels increase the risk of atherosclerosis. Statins and bile-acid sequestrants are effective LDL-lowering therapies for many patients. Development of alternative therapies remains important for patients with adverse reactions to conventional therapy, with defects in the LDL receptor-dependent lipoprotein uptake pathway and for intervention in children. Editing of apoB mRNA by the enzyme APOBEC-1 changes a glutamine codon to a stop codon, leading to the synthesis and secretion of apoB48-containing VLDL, which are rapidly cleared before they can be metabolized to LDL. Human liver does not edit apoB mRNA because it does not express APOBEC-1. Although initially promising, enthusiasm for apobec-1 gene therapy for hypercholesterolemia was blunted by the finding that uncontrolled transgenic expression of APOBEC-1 led to nonspecific editing of mRNAs and pathology. We demonstrate that APOBEC-1 fused to TAT entered primary hepatocytes, where it induced a transient increase in mRNA editing activity and enhanced synthesis and secretion of VLDL containing apoB48. Protein transduction of APOBEC-1 transiently stimulated high levels of apoB mRNA editing in a dose-dependent manner without loss of fidelity. These results suggested that apoB mRNA editing should be re-evaluated as a LDL-lowering therapeutic target in the new context of protein transduction therapy.
journal_name
Mol Pharmacoljournal_title
Molecular pharmacologyauthors
Yang Y,Ballatori N,Smith HCdoi
10.1124/mol.61.2.269keywords:
subject
Has Abstractpub_date
2002-02-01 00:00:00pages
269-76issue
2eissn
0026-895Xissn
1521-0111journal_volume
61pub_type
杂志文章abstract：:The peripheral cannabinoid receptor (CB2) is a G protein-coupled receptor that is both positively and negatively coupled to the mitogen-activated protein kinase (MAPK) and cAMP pathways, respectively, through a Bordetella pertussis toxin-sensitive G protein. CB2 receptor-transfected Chinese hamster ovary cells exhibit...
journal_title：Molecular pharmacology
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journal_title：Molecular pharmacology
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doi：
更新日期：1994-08-01 00:00:00
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journal_title：Molecular pharmacology
pub_type： 杂志文章
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journal_title：Molecular pharmacology
pub_type： 杂志文章,评审
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journal_title：Molecular pharmacology
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journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1996-02-01 00:00:00
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pub_type： 杂志文章
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journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1983-05-01 00:00:00
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journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.51.4.644
更新日期：1997-04-01 00:00:00
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journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.104.008284
更新日期：2005-05-01 00:00:00
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pub_type： 杂志文章
doi：10.1124/mol.65.2.381
更新日期：2004-02-01 00:00:00
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journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.108.047670
更新日期：2008-11-01 00:00:00
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journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.61.5.1124
更新日期：2002-05-01 00:00:00
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pub_type： 杂志文章
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更新日期：2000-07-01 00:00:00
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更新日期：2008-02-01 00:00:00
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journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1991-01-01 00:00:00
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pub_type： 杂志文章
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pub_type： 杂志文章
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更新日期：2010-05-01 00:00:00
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journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1991-11-01 00:00:00
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pub_type： 杂志文章
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更新日期：2011-06-01 00:00:00
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journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1994-10-01 00:00:00
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journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1996-08-01 00:00:00
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journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：2001-09-01 00:00:00
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更新日期：2010-02-01 00:00:00
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journal_title：Molecular pharmacology
pub_type： 杂志文章
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更新日期：2014-01-01 00:00:00
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journal_title：Molecular pharmacology
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更新日期：2012-03-01 00:00:00
