Role Of Transmembrane 141 in Cholesterol Metabolism
Main Author: | |
---|---|
Language: | English |
Published: |
Kent State University / OhioLINK
2014
|
Subjects: | |
Online Access: | http://rave.ohiolink.edu/etdc/view?acc_num=kent1416142859 |
id |
ndltd-OhioLink-oai-etd.ohiolink.edu-kent1416142859 |
---|---|
record_format |
oai_dc |
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 |
_version_ |
1719437148252274688 |