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Phospholipase A(2)-modified low-density lipoprotein activates liver X receptor in human macrophages.
Cell Biochem Biophys. 2012 Jun; 63(2):143-9.CB

Abstract

Macrophages respond to cholesterol accumulation by increasing cholesterol efflux, which is mediated by activation of the nuclear liver X receptor (LXR) and ATP binding cassette (ABC) transporters. In the present study, we investigated whether foam cell formation induced by phospholipase A(2)-modified low-density lipoprotein (PLA-LDL) influences LXR activity and cholesterol efflux in primary human monocyte-derived macrophages (MDMs). Macrophages were treated with PLA-LDL and expression of the LXR target genes ABCA1 and ABCG1 was analyzed by quantitative PCR and western blot. PLA-LDL time-dependently up-regulated ABCA1 and ABCG1 mRNA and protein. Removal of non-esterified fatty acids from PLA-LDL particles did not influence the induction of ABC transporters. A role of LXR in PLA-LDL-stimulated ABCG1 expression was verified by LXR-knockdown and luciferase reporter assays using a construct containing a LXR response element from the ABCG1 gene. Functionally, cholesterol efflux to apolipoprotein A-I and high-density lipoprotein was higher in PLA-LDL treated cells compared to controls. Together, these results demonstrate that in primary human MDMs PLA-LDL induces ABC transporter expression via LXR activation. A concomitantly increased cholesterol efflux may prevent excessive cholesterol accumulation and thus, attenuate foam cell formation.

Authors+Show Affiliations

Faculty of Medicine, Institute of Biochemistry I/ZAFES, Goethe-University Frankfurt, Theodor-Stern-Kai 7, 60590, Frankfurt, Germany.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22367754

Citation

Morbitzer, Daniel, et al. "Phospholipase A(2)-modified Low-density Lipoprotein Activates Liver X Receptor in Human Macrophages." Cell Biochemistry and Biophysics, vol. 63, no. 2, 2012, pp. 143-9.
Morbitzer D, Namgaladze D, Brüne B. Phospholipase A(2)-modified low-density lipoprotein activates liver X receptor in human macrophages. Cell Biochem Biophys. 2012;63(2):143-9.
Morbitzer, D., Namgaladze, D., & Brüne, B. (2012). Phospholipase A(2)-modified low-density lipoprotein activates liver X receptor in human macrophages. Cell Biochemistry and Biophysics, 63(2), 143-9. https://doi.org/10.1007/s12013-012-9351-4
Morbitzer D, Namgaladze D, Brüne B. Phospholipase A(2)-modified Low-density Lipoprotein Activates Liver X Receptor in Human Macrophages. Cell Biochem Biophys. 2012;63(2):143-9. PubMed PMID: 22367754.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Phospholipase A(2)-modified low-density lipoprotein activates liver X receptor in human macrophages. AU - Morbitzer,Daniel, AU - Namgaladze,Dmitry, AU - Brüne,Bernhard, PY - 2012/2/28/entrez PY - 2012/3/1/pubmed PY - 2012/9/5/medline SP - 143 EP - 9 JF - Cell biochemistry and biophysics JO - Cell Biochem Biophys VL - 63 IS - 2 N2 - Macrophages respond to cholesterol accumulation by increasing cholesterol efflux, which is mediated by activation of the nuclear liver X receptor (LXR) and ATP binding cassette (ABC) transporters. In the present study, we investigated whether foam cell formation induced by phospholipase A(2)-modified low-density lipoprotein (PLA-LDL) influences LXR activity and cholesterol efflux in primary human monocyte-derived macrophages (MDMs). Macrophages were treated with PLA-LDL and expression of the LXR target genes ABCA1 and ABCG1 was analyzed by quantitative PCR and western blot. PLA-LDL time-dependently up-regulated ABCA1 and ABCG1 mRNA and protein. Removal of non-esterified fatty acids from PLA-LDL particles did not influence the induction of ABC transporters. A role of LXR in PLA-LDL-stimulated ABCG1 expression was verified by LXR-knockdown and luciferase reporter assays using a construct containing a LXR response element from the ABCG1 gene. Functionally, cholesterol efflux to apolipoprotein A-I and high-density lipoprotein was higher in PLA-LDL treated cells compared to controls. Together, these results demonstrate that in primary human MDMs PLA-LDL induces ABC transporter expression via LXR activation. A concomitantly increased cholesterol efflux may prevent excessive cholesterol accumulation and thus, attenuate foam cell formation. SN - 1559-0283 UR - https://www.unboundmedicine.com/medline/citation/22367754/Phospholipase_A_2__modified_low_density_lipoprotein_activates_liver_X_receptor_in_human_macrophages_ L2 - https://dx.doi.org/10.1007/s12013-012-9351-4 DB - PRIME DP - Unbound Medicine ER -