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Characterization of a naturally occurring new version of the cholesterol ester transfer protein (CETP) from small intestine

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Abstract

The cholesterol ester transfer protein (CETP) is found in plasma mediating the transfer of cholesterol esters and triacylglycerides between lipoproteins. The last 26 amino acids of its carboxy-end correspond to an amphipathic α-helix whose hydrophobic side has been directly involved in the transfer of lipids [1–3]. Alterations in this region lead to the reduction or loss of lipid transfer activity [3–5]. To date, the only variant of the CETP messenger that has been reported lacks exon 9 [6–8], which translates into an inactive isoform regarding neutral lipid transfer [6–8]. In this study, we describe a new version of the messenger RNA of rabbit CETP identified exclusively in the small intestine of wild type (WT) rabbits. This isoform includes several of the intron bases prior to exon 16. The presence of a stop codon within this sequence prevents translation of exon 16, substituting the original carboxy-end sequence and therefore generating a random structure that does not contain the region responsible for neutral lipid transfer. Antibodies generated against a peptide within the carboxy-end sequence of the new isoform show the presence of this new protein in human plasma.

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References

  1. Matsunaga A, Araki K, Moriyama K, Handa K, Arakawa F, Nishi K, Sasaki J, Arakawa K: Detection of a point mutation in cholesterol ester transfer protein gene by polymerase chain reaction-mediated site-directed mutagenesis. Biochim Biophys Acta 1166: 131-134, 1993

    Google Scholar 

  2. Wang S, Kussie P, Deng L, Tall A: Defective binding of neutral lipids by carboxyl-terminal deletion mutant of cholesterol ester transfer protein. J Biol Chem 270: 612-618, 1993

    Google Scholar 

  3. Bolaños-García VM, Soriano-García M, Mas-Oliva J: Stability of the C-terminal peptide of CETP mediated trough an (i, i+4) array. Biochim Biophys Acta 1384: 7-15, 1998

    Google Scholar 

  4. Tall A: Plasma lipid transfer proteins. Annu Rev Biochem 64: 235-257, 1995

    Google Scholar 

  5. Saito K, Kobori K, Hashimoto H, Ito S, Manabe M, Yokoyama S: Epitope mapping for the anti-rabbit cholesteryl ester transfer protein monoclonal antibody that selectively inhibits triglyceride transfer. J Lipid Res 40: 2013-2021, 1999

    Google Scholar 

  6. Inazu A, Quinet EM, Wang S, Brown ML, Stevenson S, Barr ML, Moulin P, Tall AR: Alternative splicing of the mRNA encoding the human cholesterol ester transfer protein. Biochemistry 31: 2352-2358, 1992

    Google Scholar 

  7. Quinet E, Yang TP, Marinos C, Tall A: Inhibition of the cellular secretion of cholesterol ester transfer protein by a variant protein formed by alternative splicing of mRNA. J Biol Chem 268: 16891-16894, 1993

    Google Scholar 

  8. Yang TP, Agellon LB, Walsh A, Breslow JL, Tall AR: Alternative splicing oh the human cholesterol transfer protein in transgenic mice. J Biol Chem 271: 12603-12609, 1996

    Google Scholar 

  9. Stevenson SC, Wang S, Deng L, Tall A: Human plasma cholesterol ester transfer protein consists of a mixture of two forms reflecting variable glycosilation at Aspargine 341. Biochemistry 32: 5121-5126, 1993

    Google Scholar 

  10. Nagashima M, McLean J, Lawn R J: Cloning and mRNA tissue distribution of rabbit cholesterol ester transfer protein. J Lipid Res 29: 1643-1649, 1988

    Google Scholar 

  11. Ko KW, Oikawa K, Ohnishi T, Kay CM, Yokoyama S: Purification, characterization, and conformational analysis of rabbit plasma lipid transfer protein. Biochemistry 32: 6629-6636, 1993

    Google Scholar 

  12. Kotake H, Agellon LB, Yokoyama S: Modification of the N-terminal cysteine of plasma cholesterol ester transfer protein selectively inhibits triglyceride transfer activity. Biochim Biophys Acta 1347: 69-74, 1997

    Google Scholar 

  13. Bolaños-García VM, Soriano-García M, Mas-Oliva J: CETP and exchangeable apoproteínas: Common features in lipid binding activity. Mol Cell Biochem 175: 1-10, 1997

    Google Scholar 

  14. Agellon LB, Quinet EM, Gillette TG, Drayna DT, Brown ML, Tall AR: Organization of the human cholesterol ester transfer protein gene. Biochemistry 29: 1372-1376, 1990

    Google Scholar 

  15. Jiang XC, Moulin P, Quinet E, Goldberg IJ, Yacoub LK, Agellon LB, Compton D, Schnitzer-Polokoff R, Tall AR: Mammalian adipose tissue and muscle are major sources of lipid transfer protein mRNA. J Biol Chem 266: 4631-4639, 1991

    Google Scholar 

  16. Wallace AJ, Mann JI, Sutherland WH, Williams S, Chisholm A, Skeaff CM, Gudnason V, Talmud PJ, Humphries SE: Variants in the cholesterol ester transfer protein and lipoprotein lipase genes are predictors of plasma cholesterol response to dietary change. Atherosclerosis 152: 327-336, 2000

    Google Scholar 

  17. Drayna D, Jarnagin AS, McLean J, Henzel W, Khor W, Fielding C, Lawn R: Cloning and sequencing of human cholesterol ester transfer protein cDNA. Nature 327: 632-634, 1987

    Google Scholar 

  18. Sumiwaka K, Parker I, Miledi R: Expression of neurotransmitter receptors and voltage-activated channel from brain mRNA in Xenopus oocytes. In: M. Conn (ed). Methods in Neurosciences. Academic Press, Orlando, 1989, pp 30-45

    Google Scholar 

  19. Appletquis SE, Keyna U, Calvin MR, Beck-Engeser GB, Raman C, Lawn R: Sequence of the rabbit glyceraldehydes-3-phosphate dehydrogenase-encoding cDNA. Gene 163: 325-326, 1995

    Google Scholar 

  20. Brown ML, Inazu A, Hesler CB, Agellon LB, Mann C, Whitlock ME, Marcel YL, Milne RW, Koizumi J, Mabuchi H et al.: Molecular basis of lipid transfer protein deficiency in a family with increased high-density lipoproteins. Nature 342: 448-451, 1989

    Google Scholar 

  21. Lagrost L: Regulation of cholesterol ester transfer protein (CETP) activity, review of in vitro an in vivo studies. Biochim Biophys Acta 1215: 209-236, 1994

    Google Scholar 

  22. Gotoda T, Kinoshita M, Shimano H, Harada K, Shimada M, Ohsuga J, Teramoto T, Yazaki Y, Yamada N: Cholesteryl ester transfer protein deficiency caused by a nonsense mutation detected in the patient's macrophage mRNA. Biochem Biophys Res Commun 194: 519-524, 1993

    Google Scholar 

  23. Sakai N, Santamarina-Fojo S, Yamashita S, Matsuzawa Y, Brewer HB: Exon 10 skipping caused by intron 10 splice donor site mutation in cholesteryl ester transfer protein gene results in abnormal downstream splice site selection. J Lipid Res 37: 2065-2073, 1996

    Google Scholar 

  24. Takahashi K, Jiang XC, Sakai N, Yamashita S, Hirano K, Bujo H, Yamazaki H, Kusunoki, J, Miura T, Kussie P, Matsuzawa Y, Saito Y, Tall A: A missense mutation in the cholesteryl ester transfer protein gene with possible dominant effects on plasma high density lipoproteins. J Clin Invest 92: 2060-2064, 1993

    Google Scholar 

  25. Yamashita S, Hirano K, Sakai N, Matsuzawa Y: Molecular biology and pathophysiological aspects of plasma cholesteryl ester transfer protein. Biochim Biophys Acta 1529: 257-275, 2000

    Google Scholar 

  26. Pattnaik NM, Zilversmit DB: Interaction of cholesterol ester exchange protein with human plasma lipoproteins and phospholipid vesicles. J Biol Chem 254: 2782-2786, 1979

    Google Scholar 

  27. Abbey M, Bastiras S, Calvert GD: Immunoprecipitation of lipid transfer protein activity by an antibody against human plasma lipid transfer protein-I. Biochim Biophys Acta 833: 25-33 1985

    Google Scholar 

  28. Hesler CB, Tall AR, Swenson TL, Weech PK, Marcel YL, Milne RW: Monoclonal antibodies to the Mr 74,000 cholesterol ester transfer protein neutralize all of the cholesterol ester and triglyceride transfer activities in human plasma. J Biol Chem 263: 5020-5023, 1988

    Google Scholar 

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Alonso, A.L., Zentella-Dehesa, A. & Mas-Oliva, J. Characterization of a naturally occurring new version of the cholesterol ester transfer protein (CETP) from small intestine. Mol Cell Biochem 245, 173–182 (2003). https://doi.org/10.1023/A:1022832531473

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