HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Feng, J. Articles by Nicholson, A. C. Search for Related Content PubMed PubMed Citation Articles by Feng, J. Articles by Nicholson, A. C. Social Bookmarking                      What's this?

Journal of Lipid Research, Vol. 41, 688-696, May 2000
Copyright © 2000 by Lipid Research, Inc.

Original Article

Induction of CD36 expression by oxidized LDL and IL-4 by a common signaling pathway dependent on protein kinase C and PPAR-

Correspondence to: Andrew C. Nicholson

CD36, a class B scavenger receptor, is a macrophage receptor for oxidized low density lipoprotein (OxLDL) and may play a critical role in atherosclerotic foam cell formation. We have previously demonstrated that OxLDL, macrophage-colony stimulating factor (M-CSF), and interleukin-4 (IL-4) enhanced expression of CD36. The effect of OxLDL on CD36 is due, in part, to its ability to activate the transcription factor, PPAR- (peroxisome proliferator activated receptor-). Other PPAR- ligands (15-deoxy^12,14 prostaglandin J₂ (15d-PGJ₂) and the thiazolidinedione class of antidiabetic drugs) also increase CD36 expression. We have now evaluated signaling pathways involved in the induction of CD36. Treatment of RAW264.7 cells (a murine macrophage cell line) with protein kinase C (PKC) activators (diacylglycerol and ingenol) up-regulated CD36 mRNA expression. Specific inhibitors of PKC reduced CD36 expression in a time-dependent manner, while protein kinase A (PKA) and cyclic AMP agonists had no effect on CD36 mRNA expression. PKC inhibitors reduced basal expression of CD36 and blocked induction of CD36 mRNA by 15d-PGJ₂, OxLDL and IL-4. In addition, PKC inhibitors decreased both PPAR- mRNA and protein expression and blocked induction of CD36 protein surface expression by OxLDL and 15d-PGJ₂ in human monocytes, as determined by FACS. 15d-PGJ₂ had no effect on translocation of PKC- from the cytosol to the plasma membrane.

These results demonstrate that two divergent physiological or pathophysiological agonists utilize a common pathway to up-regulate of CD36 gene expression. This pathway involves initial activation of PKC with subsequent PPAR- activation. Defining these signaling pathways is critical for understanding and modulating expression of this scavenger receptor pathway.—Feng, J., J. Han, S. F. A. Pearce, R. L. Silverstein, A. M. Gotto, Jr., D. P. Hajjar, and A. C. Nicholson. Induction of CD36 expression by oxidized LDL and IL-4 by a common signaling pathway dependent on protein kinase C and PPAR-. J. Lipid Res. 2000. 41: 688;–696.

Supplementary key words: CD36, macrophage, scavenger receptor, PKC, PPAR-

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				E. Osto, A. Kouroedov, P. Mocharla, A. Akhmedov, C. Besler, L. Rohrer, A. von Eckardstein, S. Iliceto, M. Volpe, T. F. Luscher, et al. Inhibition of Protein Kinase C{beta} Prevents Foam Cell Formation by Reducing Scavenger Receptor A Expression in Human Macrophages Circulation, November 18, 2008; 118(21): 2174 - 2182. [Abstract] [Full Text] [PDF]

				V. L. King, L. A. Cassis, and A. Daugherty Interleukin-4 Does Not Influence Development of Hypercholesterolemia or Angiotensin II-Induced Atherosclerotic Lesions in Mice Am. J. Pathol., December 1, 2007; 171(6): 2040 - 2047. [Abstract] [Full Text] [PDF]

				S. Collot-Teixeira, J. Martin, C. McDermott-Roe, R. Poston, and J. L. McGregor CD36 and macrophages in atherosclerosis Cardiovasc Res, August 1, 2007; 75(3): 468 - 477. [Abstract] [Full Text] [PDF]

				S. Cho, H. H. Szeto, E. Kim, H. Kim, A. T. Tolhurst, and J. T. Pinto A Novel Cell-permeable Antioxidant Peptide, SS31, Attenuates Ischemic Brain Injury by Down-regulating CD36 J. Biol. Chem., February 16, 2007; 282(7): 4634 - 4642. [Abstract] [Full Text] [PDF]

				E. L. Bradshaw, X.-A. Li, T. Guerin, W. V. Everson, M. E. Wilson, A. J. Bruce-Keller, R. N. Greenberg, L. Guo, S. A. Ross, and E. J. Smart Nucleoside reverse transcriptase inhibitors prevent HIV protease inhibitor-induced atherosclerosis by ubiquitination and degradation of protein kinase C Am J Physiol Cell Physiol, December 1, 2006; 291(6): C1271 - C1278. [Abstract] [Full Text] [PDF]

				J. P. Conway and M. Kinter Dual Role of Peroxiredoxin I in Macrophage-derived Foam Cells J. Biol. Chem., September 22, 2006; 281(38): 27991 - 28001. [Abstract] [Full Text] [PDF]

				A. Puig-Kroger, A. Dominguez-Soto, L. Martinez-Munoz, D. Serrano-Gomez, M. Lopez-Bravo, E. Sierra-Filardi, E. Fernandez-Ruiz, N. Ruiz-Velasco, C. Ardavin, Y. Groner, et al. RUNX3 Negatively Regulates CD36 Expression in Myeloid Cell Lines J. Immunol., August 15, 2006; 177(4): 2107 - 2114. [Abstract] [Full Text] [PDF]

				N. Takeda, I. Manabe, T. Shindo, H. Iwata, S. Iimuro, H. Kagechika, K. Shudo, and R. Nagai Synthetic Retinoid Am80 Reduces Scavenger Receptor Expression and Atherosclerosis in Mice by Inhibiting IL-6 Arterioscler Thromb Vasc Biol, May 1, 2006; 26(5): 1177 - 1183. [Abstract] [Full Text] [PDF]

				A. Munteanu, M. Taddei, I. Tamburini, E. Bergamini, A. Azzi, and J.-M. Zingg Antagonistic Effects of Oxidized Low Density Lipoprotein and {alpha}-Tocopherol on CD36 Scavenger Receptor Expression in Monocytes: INVOLVEMENT OF PROTEIN KINASE B AND PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR-{gamma} J. Biol. Chem., March 10, 2006; 281(10): 6489 - 6497. [Abstract] [Full Text] [PDF]

				N. Ide, C. Keller, and N. Weiss Aged Garlic Extract Inhibits Homocysteine-Induced CD36 Expression and Foam Cell Formation in Human Macrophages J. Nutr., March 1, 2006; 136(3): 755S - 758S. [Abstract] [Full Text] [PDF]

				A. Daugherty, N. R. Webb, D. L. Rateri, and V. L. King Thematic review series: The Immune System and Atherogenesis. Cytokine regulation of macrophage functions in atherogenesis J. Lipid Res., September 1, 2005; 46(9): 1812 - 1822. [Abstract] [Full Text] [PDF]

				C. Rask-Madsen and G. L. King Proatherosclerotic Mechanisms Involving Protein Kinase C in Diabetes and Insulin Resistance Arterioscler Thromb Vasc Biol, March 1, 2005; 25(3): 487 - 496. [Abstract] [Full Text] [PDF]

				A. S. Major, M. T. Wilson, J. L. McCaleb, Y. Ru Su, A. K. Stanic, S. Joyce, L. Van Kaer, S. Fazio, and M. F. Linton Quantitative and Qualitative Differences in Proatherogenic NKT Cells in Apolipoprotein E-Deficient Mice Arterioscler Thromb Vasc Biol, December 1, 2004; 24(12): 2351 - 2357. [Abstract] [Full Text] [PDF]

				R. Stocker and J. F. Keaney Jr. Role of Oxidative Modifications in Atherosclerosis Physiol Rev, October 1, 2004; 84(4): 1381 - 1478. [Abstract] [Full Text] [PDF]

				R. F. Klein, J. Allard, Z. Avnur, T. Nikolcheva, D. Rotstein, A. S. Carlos, M. Shea, R. V. Waters, J. K. Belknap, G. Peltz, et al. Regulation of Bone Mass in Mice by the Lipoxygenase Gene Alox15 Science, January 9, 2004; 303(5655): 229 - 232. [Abstract] [Full Text] [PDF]

				L. Sun, A. C. Nicholson, D. P. Hajjar, A. M. Gotto Jr., and J. Han Adipogenic differentiating agents regulate expression of fatty acid binding protein and CD36 in the J744 macrophage cell line J. Lipid Res., October 1, 2003; 44(10): 1877 - 1886. [Abstract] [Full Text] [PDF]

				H. M. Wilmsen, T. P. Ciaraldi, L. Carter, N. Reehman, S. R. Mudaliar, and R. R. Henry Thiazolidinediones upregulate impaired fatty acid uptake in skeletal muscle of type 2 diabetic subjects Am J Physiol Endocrinol Metab, August 1, 2003; 285(2): E354 - E362. [Abstract] [Full Text] [PDF]

				F. Sennlaub, F. Valamanesh, A. Vazquez-Tello, A.M. El-Asrar, D. Checchin, S. Brault, F. Gobeil, M.H. Beauchamp, B. Mwaikambo, Y. Courtois, et al. Cyclooxygenase-2 in Human and Experimental Ischemic Proliferative Retinopathy Circulation, July 15, 2003; 108(2): 198 - 204. [Abstract] [Full Text] [PDF]

				J. H. Von der Thusen, J. Kuiper, T. J. C. Van Berkel, and E. A. L. Biessen Interleukins in Atherosclerosis: Molecular Pathways and Therapeutic Potential Pharmacol. Rev., March 1, 2003; 55(1): 133 - 166. [Abstract] [Full Text] [PDF]

				C.A. Argmann, C.G. Sawyez, C.J. McNeil, R.A. Hegele, and M.W. Huff Activation of Peroxisome Proliferator-Activated Receptor Gamma and Retinoid X Receptor Results in Net Depletion of Cellular Cholesteryl Esters in Macrophages Exposed to Oxidized Lipoproteins Arterioscler Thromb Vasc Biol, March 1, 2003; 23(3): 475 - 482. [Abstract] [Full Text] [PDF]

				Z. Zou, C. C. DiRusso, V. Ctrnacta, and P. N. Black Fatty Acid Transport in Saccharomyces cerevisiae. DIRECTED MUTAGENESIS OF FAT1 DISTINGUISHES THE BIOCHEMICAL ACTIVITIES ASSOCIATED WITH Fat1p J. Biol. Chem., August 16, 2002; 277(34): 31062 - 31071. [Abstract] [Full Text] [PDF]

				T. E. Akiyama, S. Sakai, G. Lambert, C. J. Nicol, K. Matsusue, S. Pimprale, Y.-H. Lee, M. Ricote, C. K. Glass, H. B. Brewer Jr., et al. Conditional Disruption of the Peroxisome Proliferator-Activated Receptor {gamma} Gene in Mice Results in Lowered Expression of ABCA1, ABCG1, and apoE in Macrophages and Reduced Cholesterol Efflux Mol. Cell. Biol., April 15, 2002; 22(8): 2607 - 2619. [Abstract] [Full Text] [PDF]

				M.-C. Beauchamp and G. Renier Homocysteine Induces Protein Kinase C Activation and Stimulates c-Fos and Lipoprotein Lipase Expression in Macrophages Diabetes, April 1, 2002; 51(4): 1180 - 1187. [Abstract] [Full Text] [PDF]

				C. E. Clay, G.-i. Atsumi, K. P. High, and F. H. Chilton Early de Novo Gene Expression Is Required for 15-Deoxy-Delta 12,14-prostaglandin J2-induced Apoptosis in Breast Cancer Cells J. Biol. Chem., December 7, 2001; 276(50): 47131 - 47135. [Abstract] [Full Text] [PDF]

				C. A. Argmann, C. H. Van Den Diepstraten, C. G. Sawyez, J. Y. Edwards, R. A. Hegele, B. M. Wolfe, and M. W. Huff Transforming Growth Factor-{beta}1 Inhibits Macrophage Cholesteryl Ester Accumulation Induced by Native and Oxidized VLDL Remnants Arterioscler Thromb Vasc Biol, December 1, 2001; 21(12): 2011 - 2018. [Abstract] [Full Text] [PDF]

				S. Devaraj, I. Hugou, and I. Jialal {{alpha}}-Tocopherol decreases CD36 expression in human monocyte-derived macrophages J. Lipid Res., April 1, 2001; 42(4): 521 - 527. [Abstract] [Full Text]

				Z. Chen, S. Ishibashi, S. Perrey, J.-i. Osuga, T. Gotoda, T. Kitamine, Y. Tamura, H. Okazaki, N. Yahagi, Y. Iizuka, et al. Troglitazone Inhibits Atherosclerosis in Apolipoprotein E-Knockout Mice : Pleiotropic Effects on CD36 Expression and HDL Arterioscler Thromb Vasc Biol, March 1, 2001; 21(3): 372 - 377. [Abstract] [Full Text] [PDF]

				J. B. Giardina, D. J. Tanner, and R. A. Khalil Oxidized-LDL Enhances Coronary Vasoconstriction by Increasing the Activity of Protein Kinase C Isoforms {{alpha}} and {{epsilon}} Hypertension, February 1, 2001; 37(2): 561 - 568. [Abstract] [Full Text] [PDF]

				S. S. Davies, A. V. Pontsler, G. K. Marathe, K. A. Harrison, R. C. Murphy, J. C. Hinshaw, G. D. Prestwich, A. St. Hilaire, S. M. Prescott, G. A. Zimmerman, et al. Oxidized Alkyl Phospholipids Are Specific, High Affinity Peroxisome Proliferator-activated Receptor gamma Ligands and Agonists J. Biol. Chem., May 4, 2001; 276(19): 16015 - 16023. [Abstract] [Full Text] [PDF]