Inhibition of ABCA1 Protein Expression and Cholesterol Efflux by TNF α in MLO-Y4 Osteocytes

Kent R Wehmeier; William Kurban; Chandrikha Chandrasekharan; Luisa Onstead-Haas; Arshag D Mooradian; Michael J Haas

doi:10.1007/s00223-015-0106-2

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Inhibition of ABCA1 Protein Expression and Cholesterol Efflux by TNF α in MLO-Y4 Osteocytes

Journal article

Peer reviewed

Inhibition of ABCA1 Protein Expression and Cholesterol Efflux by TNF α in MLO-Y4 Osteocytes

Kent R Wehmeier, William Kurban, Chandrikha Chandrasekharan, Luisa Onstead-Haas, Arshag D Mooradian and Michael J Haas

Calcified tissue international, Vol.98(6), pp.586-595

06/2016

DOI: 10.1007/s00223-015-0106-2

PMID: 26759003

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Abstract

Hip fracture and myocardial infarction cause significant morbidity and mortality. In vivo studies raising serum cholesterol levels as well as pro-inflammatory cytokines such as TNF α manifest bone loss and atherosclerotic vascular disease, suggesting that abnormalities of cholesterol transport may contribute to osteoporosis. We used the mouse osteocyte cell line (MLO-Y4) to investigate the effects of TNF α on the expression of cholesterol acceptor proteins such as apolipoprotein A-I (apo A-I) and apolipoprotein E (apo E), as well as on the cholesterol transporters ATP-binding cassette-1 (ABCA1), scavenger receptor class B type 1 (SRB1), and cluster of differentiation 36 (CD36). MLO-Y4 cells do not express apo A-I or apo E; however, they do express all three cholesterol transporters (ABCA1, SRB1, and CD36). Treatment of MLO-Y4 cells with TNF α had no effect on SRB1, CD36, and osteocalcin levels; however, TNF α reduced ABCA1 protein levels in a dose-dependent manner and cholesterol efflux to apo A-I. Interestingly, TNF α treatment increased ABCA1 promoter activity and ABCA1 mRNA levels, and increased liver X receptor α protein expression, but had no effect on retinoid X receptor α and retinoic acid receptor α levels. Pharmacological inhibition of p38 mitogen-activated protein (MAP) kinase, but not c-jun-N-terminal kinase 1 or mitogen-activated protein kinase (MEK), restored ABCA1 protein levels in TNF α-treated cells. These results suggest that pro-inflammatory cytokines regulate cholesterol metabolism in osteocytes in part by suppressing ABCA1 levels post-translationally in a p38 MAP kinase-dependent manner.

Animals

ATP Binding Cassette Transporter 1 - biosynthesis

Blotting, Western

CD36 Antigens - metabolism

Cell Line

Cholesterol - metabolism

Mice

Osteocytes - metabolism

Real-Time Polymerase Chain Reaction

Scavenger Receptors, Class B - metabolism

Transfection

Tumor Necrosis Factor-alpha - metabolism

Tumor Necrosis Factor-alpha - pharmacology

Details

Title: Subtitle: Inhibition of ABCA1 Protein Expression and Cholesterol Efflux by TNF α in MLO-Y4 Osteocytes
Creators: Kent R Wehmeier - Florida College
William Kurban - Florida College
Chandrikha Chandrasekharan - Florida College
Luisa Onstead-Haas - Florida College
Arshag D Mooradian - Florida College
Michael J Haas - Florida College
Resource Type: Journal article
Publication Details: Calcified tissue international, Vol.98(6), pp.586-595
DOI: 10.1007/s00223-015-0106-2
PMID: 26759003
ISSN: 0171-967X
eISSN: 1432-0827
Grant note: name: University of Florida Jacksonville
Language: English
Date published: 06/2016
Academic Unit: Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
Record Identifier: 9984359771102771

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