Role Of Transmembrane 141 in Cholesterol Metabolism

Role Of Transmembrane 141 in Cholesterol Metabolism

Bibliographic Details
Main Author: Al-Khfajy, Wrood Salim Dawood
Language:English
Published: Kent State University / OhioLINK 2014
Subjects:
Pharmacology
TMEM 141
ATP binding cassette transporter A1
lipid homeostasis
high-density lipoprotein
reverse cholesterol transport
Online Access:http://rave.ohiolink.edu/etdc/view?acc_num=kent1416142859
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spelling ndltd-OhioLink-oai-etd.ohiolink.edu-kent14161428592021-08-03T06:27:54Z Role Of Transmembrane 141 in Cholesterol Metabolism Al-Khfajy, Wrood Salim Dawood Pharmacology TMEM 141 ATP binding cassette transporter A1 lipid homeostasis high-density lipoprotein reverse cholesterol transport Wrood Salim Al-Khfajy, M.A., December 2014 PharmacologyRole of Transmembrane 141 in Cholesterol MetabolismThesis Advisor: Yanqiao ZhangTMEM141 belongs to the large family of transmembrane (TMEM) proteins, and its physiological role remains largely unknown. In our study, we found that hepatic Tmem141 expression is markedly induced by FXR and repressed in db/db or high fat diet-fed mice. We determined the effect of acute loss or augmentation of hepatic Tmem141 function on cholesterol homeostasis. We generated adenovirus expressing LacZ (Ad-shLacZ) or small hairpin RNA of Tmem141 (Ad-shTmem141). Hepatic knockdown of Tmem141 markedly reduced hepatic Tmem141 expression and resulted in striking phenotypes, including a >8-fold decrease in total plasma cholesterol and a >80% decrease in HDL-C and LDL-C. Consistent with the loss-of-function data, Tmem141 deficiency reduces ABCA1 expression in human hepatic (Huh-7) cells, and macrophages and mouse hepatocytes, and causes impaired cholesterol efflux in both macrophages and hepatocytes. Interestingly, mice overexpressing hepatic Tmem141 had unchanged plasma cholesterol levels and ABCA1 expression. Co- immunoprecipitation assays demonstrate a direct interaction between Tmem141 and ABCA1. Finally, in vitro study revealed that Tmem141 is ubiquitously expressed and localizes mainly to endocytic compartments where it may regulate ABCA1 degradation/recycling. In summary, we have identified Tmem141 as a novel posttranscriptional regulator of ABCA1 expression and cellular cholesterol homeostasis, a better understanding of the pathways, cells use to initiate HDL assembly is necessary to design novel therapies to increase HDL formation clinically to reduce cellular cholesterol pool by promoting reverse cholesterol transport from cells and preventing atherosclerotic vascular disease. 2014-11-19 English text Kent State University / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=kent1416142859 http://rave.ohiolink.edu/etdc/view?acc_num=kent1416142859 unrestricted This thesis or dissertation is protected by copyright: some rights reserved. It is licensed for use under a Creative Commons license. Specific terms and permissions are available from this document's record in the OhioLINK ETD Center.
collection NDLTD
language English
sources NDLTD
topic Pharmacology
TMEM 141
ATP binding cassette transporter A1
lipid homeostasis
high-density lipoprotein
reverse cholesterol transport
spellingShingle Pharmacology
TMEM 141
ATP binding cassette transporter A1
lipid homeostasis
high-density lipoprotein
reverse cholesterol transport
Al-Khfajy, Wrood Salim Dawood
Role Of Transmembrane 141 in Cholesterol Metabolism
author Al-Khfajy, Wrood Salim Dawood
author_facet Al-Khfajy, Wrood Salim Dawood
author_sort Al-Khfajy, Wrood Salim Dawood
title Role Of Transmembrane 141 in Cholesterol Metabolism
title_short Role Of Transmembrane 141 in Cholesterol Metabolism
title_full Role Of Transmembrane 141 in Cholesterol Metabolism
title_fullStr Role Of Transmembrane 141 in Cholesterol Metabolism
title_full_unstemmed Role Of Transmembrane 141 in Cholesterol Metabolism
title_sort role of transmembrane 141 in cholesterol metabolism
publisher Kent State University / OhioLINK
publishDate 2014
url http://rave.ohiolink.edu/etdc/view?acc_num=kent1416142859
work_keys_str_mv AT alkhfajywroodsalimdawood roleoftransmembrane141incholesterolmetabolism
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