Last update 01 Nov 2024

ApoB editing catalytic polypeptide

Last update 01 Nov 2024

Basic Info

Synonyms-

Introduction-

Drugs associated with ApoB editing catalytic polypeptide

IMB-2613

Target

ApoB editing catalytic polypeptide

Mechanism

ApoB editing catalytic polypeptide modulators

Active Org.

Institute of Medicinal Biotechnology Academy of Medical Scien

Originator Org.

Institute of Medicinal Biotechnology Academy of Medical Scien

Active Indication

Hepatitis B

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with ApoB editing catalytic polypeptide

100 Translational Medicine associated with ApoB editing catalytic polypeptide

0 Patents (Medical) associated with ApoB editing catalytic polypeptide

Literatures (Medical) associated with ApoB editing catalytic polypeptide

01 Oct 2008·Arteriosclerosis, Thrombosis, and Vascular BiologyQ1 · MEDICINE

Absence of Hyperlipidemia in LDL Receptor-Deficient Mice Having Apolipoprotein B100 Without the Putative Receptor-Binding Sequences

Q1 · MEDICINE

Article

Author: Johnson, Lance A. ; Altenburg, Michael K. ; Maeda, Nobuyo ; Scanga, Lori T. ; Walzem, Rosemary L.

Objective— To examine the effects of apoB100 structure, specifically a mutation in the LDLr binding region, on the production of LDL and development of atherosclerosis in vivo. Methods and Results—Ldlr−/−Apobec1−/− mice lacking the LDLR and apoB editing enzyme accumulated LDL in plasma and developed severe atherosclerosis when they had wild-type apoB100. In marked contrast, in Ldlr−/−Apobec1−/− mice carrying the Apob100-β mutation, in the 2 putative LDLR-binding domains of apoB prevented both LDL accumulation and atherosclerosis. Intestinal absorption of lipids and triglyceride secretion from the liver were not affected. However, the VLDL particles with apoB100-β were larger in volume by about 70%, and carried approximately four times as much apoE per particle. ApoB100-β synthesis rate in the primary hepatocytes was normal, but its intracellular degradation was enhanced. Additionally, mutant apoB100 VLDL cleared from the circulation more quickly in vivo through apoE-LRP-mediated mechanism than VLDL with wild-type apoB100. In contrast, uptake of the 2 VLDL by macrophages were not different. Conclusion— While conformational change to apoB100 during conversion of VLDL to LDL exposes LDLR binding domains and facilitates LDLR-mediated lipoprotein clearance, it may also inhibit LRP-mediated VLDL uptake and contribute to LDL accumulation in familial hypercholesterolemia.

01 Jan 2003·Kidney and Blood Pressure ResearchQ4 · MEDICINE

Nephropathy in a Hypercholesterolemic Mouse Model with Streptozotocin-Induced Diabetes

Q4 · MEDICINE

ArticleOA

Author: Sohn, Mimi ; Won, Wesley ; Eldridge, Leslie ; Hazen-Martin, Debra J. ; Lyons, Timothy J. ; Hammad, Samar M. ; Powell-Braxton, Lyn

Background/Aims: The contribution of preexisting hypercholesterolemia to diabetic nephropathy remains unclear. We assessed the impact of hypercholesterolemia on diabetic nephropathy using a double knockout (DKO) mouse, null for the low-density lipoprotein receptor (Ldlr–/–) and the apoB mRNA editing catalytic polypeptide 1 (Apobec1–/–). Methods: Wild-type (WT) and DKO mice received sham or streptozotocin injections at age 7 weeks, yielding control (WT-C, DKO-C) and diabetic (WT-D, DKO-D) groups. At sacrifice (age 40 weeks), albuminuria was determined by ELISA, and kidney sections were examined by light and electron microscopy. Results: Albuminuria increased in diabetic mice (WT-D: 82.4 ± 37.2 µg/18 h; DKO-D: 58.0 ± 45.7 µg/18 h) versusnondiabetic controls (WT-C: 10.2 ± 7.2 µg/18 h; DKO-C: 8.6 ± 5.3 µg/18 h) (p < 0.0001), but was unaffected by hypercholesterolemia. Light microscopy of kidney sections demonstrated increased collagen levels in glomeruli in WT-D mice, but not in DKO-D mice or either control group. Electron microscopy showed a thickened glomerular basement membrane in WT-D mice only. The proximal tubular basement membrane thickness was increased in both diabetic groups versusnondiabetic controls (p < 0.01); in WT-D mice this was attributable to collagen accumulation, but in DKO-D mice it was mainly caused by lipid vacuoles. Conclusions: In this animal model, preexisting hypercholesterolemia did not exacerbate either glomerular lesions of diabetes (collagen accumulation, basement membrane thickening) or albuminuria, but appeared to mitigate these effects. Furthermore, the combination of hypercholesterolemia and diabetes resulted in a significant lipid accumulation in the tubular basement membrane.

01 Sep 1996·Journal of Lipid ResearchQ2 · BIOLOGY

Hepatic gene transfer of the catalytic subunit of the apolipoprotein B mRNA editing enzyme results in a reduction of plasma LDL levels in normal and watanabe heritable hyperlipidemic rabbits

Q2 · BIOLOGY

Article

Author: Jayanta Roy Chowdhury ; J. Greeve ; Namita Roy Chowdhury ; V. K. Jona ; M. S. Horwitz

Apolipoprotein (apo) B exists in two forms, the full length protein apoB-100 and the carboxyterminal-truncated apoB-48 that is synthesized in the intestine due to editing of the apoB mRNA which generates a premature stop codon. To determine whether gene transfer of the catalytic subunit of the apoB mRNA editing enzyme APOBEC-1 (apoB mRNA editing enzyme catalytic polypeptide 1) into the liver of rabbits reconstitutes hepatic apoB mRNA editing and how this affects the plasma levels of apoB-containing lipoproteins, we constructed an APOBEC-1 recombinant adenovirus (Ad APOBEC-1). After injection of Ad APOBEC-1 into normal New Zealand White (NZW) or Watanabe heritable hyperlipidemic (WHHL) rabbits, up to 50% of the hepatic apoB mRNA was edited and freshly isolated hepatocytes secreted predominantly apoB-48-containing lipoproteins. VLDL isolated from Ad APOBEC-1-treated NZW and WHHL rabbits contained both apoB-100 and apoB-48, whereas that from control rabbits infected with a beta-galactosidase recombinant adenovirus (Ad LacZ) contained exclusively apoB-100. VLDL from WHHL rabbits treated with Ad APOBEC-1 had the same particle size, lipid composition, and content of apolipoprotein E as VLDL from Ad LacZ-infected control animals. An increase of VLDL was observed in NZW and WHHL rabbits after infection with Ad APOBEC-1 as well as Ad LacZ. After injection of Ad APOBEC-1, LDL became undetectable in the plasma of NZW rabbits and was reduced by an average of 65% in the plasma of WHHL rabbits compared to Ad LacZ-infected controls. LDL from Ad APOBEC-1-infected WHHL rabbits contained only apoB-100. VLDL isolated from Ad APOBEC-1-infected WHHL rabbits were rapidly cleared from the circulation after injection into NZW rabbits. These results provide further evidence that the switch in the hepatic synthesis from exclusively apoB-100 to partly apoB-48 can result in a reduction of LDL formation that requires the full-length apoB-100.

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ApoB editing catalytic polypeptide

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