Biomedical Science Letters (대한의생명과학회지)

The Korean Society for Biomedical Laboratory Sciences (대한의생명과학회)
권호 표지
DOI QR코드

DOI QR Code

Triglyceride Up-regulates Expression of ABCG1 in PMA-induced THP-1 Macrophages Through Activation of JNK and p38 MAPK Pathways

  • Lim, Jaewon (Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University) ;
  • Kim, Sung Hoon (Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University) ;
  • Kang, Yeo Wool (Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University) ;
  • Jung, Byung Chul (Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University) ;
  • Kim, Hyun-Kyung (Department of Biomedical Laboratory Science, College of Natural Science, Gimcheon University) ;
  • Lee, Juyeon (Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University) ;
  • Lee, Dongsup (Department of Clinical Laboratory Science, Hyejeon College) ;
  • Rhee, Ki-Jong (Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University) ;
  • Kim, Yoon Suk (Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University)
  • Received : 2014.12.01
  • Accepted : 2014.12.22
  • Published : 2014.12.31
Download PDF
⟨ Previous Next ⟩

Abstract

Triglyceride (TG) can cause death of macrophages and formation of foam cells thereby increasing inflammation in atherosclerotic plaques. Accumulation of cholesterol in macrophages is another critical event that promotes development of inflammatory cardiovascular diseases. Several proteins are known to transport intracellular cholesterol outside of the cell and these proteins are thought to be protective against atherosclerosis pathogenesis. It is unknown whether TG can affect cholesterol efflux in macrophages. In the current study, we examined mRNA expression levels of genes that promote efflux of cholesterol (ABCA1, ABCG1 and SR-B1). We found that TG treated THP-1 macrophages exhibited an increase in ABCG1 expression in a dose- and time-dependent manner. In contrast, the expression of ABCA1 and SR-B1 remained unchanged. To identify cell signaling pathways that participate in up-regulation of ABCG1, THP-1 macrophages were treated with various cell signaling inhibitors. We found that inhibition of the JNK and p38 MAPK pathway completely abrogated up-regulation of ABCG1 whereas inhibition of MEK1 further enhanced ABCG1 expression in TG treated THP-1 macrophages. Also, TG induced phosphorylation of JNK and p38 MAPK in THP-1 macrophages. These results suggest that TG may potentially influence cholesterol efflux in macrophages.

Keywords

References

  1. Aronis A, Madar Z, Tirosh O. Mechanism underlying oxidative stress-mediated lipotoxicity: Exposure of J774.2 macrophages to triacylglycerols facilitates mitochondrial reactive oxygen species production and cellular necrosis. Free Radical Bio Med. 2005. 38: 1221-1230. https://doi.org/10.1016/j.freeradbiomed.2005.01.015
  2. Calkin AC, Tontonoz P. Liver X receptor signaling pathways and atherosclerosis. Arterioscler Thromb Vasc Biol. 2010. 30: 1513-1518. https://doi.org/10.1161/ATVBAHA.109.191197
  3. Daniels TF, Killinger KM, Michal JJ, Wright RW, Jiang Z. Lipoproteins, cholesterol homeostasis and cardiac health. Int J Biol Sci. 2009. 5: 474-488.
  4. Dean M, Rzhetsky A, Allikmets R. The human ATP-binding cassette (ABC) transporter superfamily. Genome Res. 2001. 11: 1156-1166. https://doi.org/10.1101/gr.GR-1649R
  5. Feingold KR, Shigenaga JK, Kazemi MR, McDonald CM, Patzek SM, Cross AS, Moser A, Grunfeld C. Mechanisms of trigly-ceride accumulation in activated macrophages. J Leukoc Biol. 2012. 92: 829-839. https://doi.org/10.1189/jlb.1111537
  6. Huwait EA, Greenow KR, Singh NN, Ramji DP. A novel role for c-Jun N-terminal kinase and phosphoinositide 3-kinase in the liver X receptor-mediated induction of macrophage gene expression. Cell Signal. 2011. 23: 542-549. https://doi.org/10.1016/j.cellsig.2010.11.002
  7. Kastelein JP, Steeg WA, Holme I, Gaffney M, Cater NB, Barter P, Deedwania P, Olsson AG, Boekholdt SM, Demicco DA, Szarek M, LaRosa JC, Pedersen TR, Grundy SM. Lipids, apolipoproteins, and their ratios in relation to cardiovascular events with statin treatment. Circulation. 2008. 117: 3002-3009. https://doi.org/10.1161/CIRCULATIONAHA.107.713438
  8. Kennedy MA, Barrera GC, Nakamura K, Baldan A, Tarr P, Fishbein MC, Frank J, Francone OL, Edwards PA. ABCG1 has a critical role in mediating cholesterol efflux to HDL and preventing cellular lipid accumulation. Cell Metab. 2005. 1: 121-131. https://doi.org/10.1016/j.cmet.2005.01.002
  9. Khera AV, Cuchel M, de la Llera-Moya M, Rodrigues A, Burke MF, Jafri K, French BC, Philips JA, Mucksavage ML, Wilensky RL, Mohler ER, Rothblat GH, Rader DJ. Cholesterol efflux capacity, high-density lipoprotein function, and atherosclerosis. N Engl J Med. 2011. 364: 127-135. https://doi.org/10.1056/NEJMoa1001689
  10. Kunjathoor VV, Febbraio M, Podrez EA, Moore KJ, Andersson L, Koehn S, Rhee JS, Silverstein R, Hoff HF, Freeman MW. Scavenger receptors class A-I/II and CD36 are the principal receptors responsible for the uptake of modified low density lipoprotein leading to lipid loading in macrophages. J Biol Chem. 2002. 277: 49982-49988. https://doi.org/10.1074/jbc.M209649200
  11. Lind L. Circulating markers of inflammation and atherosclerosis. Atherosclerosis. 2003. 169: 203-214. https://doi.org/10.1016/S0021-9150(03)00012-1
  12. Moore KJ, Tabas I. Macrophages in the pathogenesis of atherosclerosis. Cell. 2011. 145: 341-355. https://doi.org/10.1016/j.cell.2011.04.005
  13. Mulay V, Wood P, Manetsch M, Darabi M, Cairns R, Hoque M, Chan KC, Reverter M, Alvarez-Guaita A, Rye KA, Rentero C, Heeren J, Enrich C, Grewal T. Inhibition of mitogenactivated protein kinase Erk1/2 promotes protein degradation of ATP binding cassette transporters A1 and G1 in CHO and HuH7 cells. PLoS One. 2013. 8: e62667. https://doi.org/10.1371/journal.pone.0062667
  14. Nagelin MH, Srinivasan S, Nadler JL, Hedrick CC. Murine 12/15-lipoxygenase regulates ATP-binding cassette transporter G1 protein degradation through p38- and JNK2-dependent pathways. J Biol Chem. 2009. 284: 31303-31314. https://doi.org/10.1074/jbc.M109.028910
  15. Palmer AM, Murphy N, Graham A. Triglyceride-rich lipoproteins inhibit cholesterol efflux to apolipoprotein (apo) A1 from human macrophage foam cells. Atherosclerosis. 2004. 173: 27-38. https://doi.org/10.1016/j.atherosclerosis.2003.12.001
  16. Repa JJ, Liang G, Ou J, Bashmakov Y, Lobaccaro JM, Shimomura I, Shan B, Brown MS, Goldstein JL, Mangelsdorf DJ. Regulation of mouse sterol regulatory element-binding protein-1c gene (SREBP-1c) by oxysterol receptors, $LXR{\alpha}$ and $LXR{\beta}$. Genes Dev. 2000. 14: 2819-2830. https://doi.org/10.1101/gad.844900
  17. Son SJ, Rhee K-J, Lim J, Kim TU, Kim TJ, Kim YS. Triglycerideinduced macrophage cell death is triggered by caspase-1. Biol Pharm Bull. 2013. 36: 108-113.
  18. Tall AR, Yvan-Charvet L, Terasaka N, Pagler T, Wang N. HDL, ABC transporters, and cholesterol efflux: implications for the treatment of atherosclerosis. Cell Metab. 2008. 7: 365-375. https://doi.org/10.1016/j.cmet.2008.03.001
  19. Tarr PT, Edwards PA. ABCG1 and ABCG4 are coexpressed in neurons and astrocytes of the CNS and regulate cholesterol homeostasis through SREBP-2. J Lipid Res. 2008. 49: 169-182. https://doi.org/10.1194/jlr.M700364-JLR200
  20. Wang N, Silver DL, Thiele C, Tall AR. ABCA1 functions as a cholesterol efflux regulatory protein. J Biol Chem. 2001. 276: 23742-23747. https://doi.org/10.1074/jbc.M102348200
  21. Yancey PG, Bortnick AE, Kellner-Weibel G, de la Llera-Moya M, Philips MC, Rothblat GH. Importance of different pathways of cellular cholesterol efflux. Arterioscler Thromb Vasc Biol. 2003. 23: 712-719. https://doi.org/10.1161/01.ATV.0000057572.97137.DD
  22. Yoon HS, Ju JH, Lee JE, Park HJ, Lee JM, Shin HK, Holzapfel W, Park KY, Doa MS. The probiotic Lactobacillus rhamnosus BFE5264 and Lactobacillus plantarum NR74 promote cholesterol efflux and suppress inflammation in THP-1 cells. J Sci Food Agric. 2012. 93: 781-787.
  23. Yvan-Charvet L, Ranalletta M, Wang N, Han S, Terasaka N, Li R, Welch C, Tall AR. Combined deficiency of ABCA1 and ABCG1 promotes foam cell accumulation and accelerates atherosclerosis in mice. J Clin Invest. 2007. 117: 3900-3908.
  24. Yvan-Charvet L, Pagler TA, Seimon TA, Thorp E, Welch CL, Witztum JL, Tabas I, Tall AR. ABCA1 and ABCG1 protect against oxidative stress-induced macrophage apoptosis during efferocytosis. Circ Res. 2010. 25: 1861-1869.