+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Differential interaction of the human cholesteryl ester transfer protein with plasma high density lipoproteins (HDLs) from humans, control mice, and transgenic mice to human HDL apolipoproteins. Lack of lipid transfer inhibitory activity in transgenic mice expressing human apoA-I



Differential interaction of the human cholesteryl ester transfer protein with plasma high density lipoproteins (HDLs) from humans, control mice, and transgenic mice to human HDL apolipoproteins. Lack of lipid transfer inhibitory activity in transgenic mice expressing human apoA-I



Journal of Biological Chemistry 272(39): 24287-24293



Plasma high density lipoproteins (HDLs) from humans, from transgenic mice to human apolipoprotein A-I (HuAITg mice), from transgenic mice to human apolipoprotein A-II (HuAIITg mice), from transgenic mice to human apolipoproteins A-I and A-II (HuAIAIITg mice), and from C57BL/6 control mice were isolated, and their ability to interact with the human cholesteryl ester transfer protein (CETP) was studied. Whereas cholesteryl ester transfer rates were gradually enhanced by the addition of moderate amounts of HDL from the different sources, striking differences appeared when HDL levels kept increasing beyond a maximal transfer value. Indeed, while a plateau value corresponding to maximal CETP activity was maintained when raising the concentration of HuAITg HDL and HuAIAIITg HDL, inhibitions could be observed with the highest levels of human, control mouse, and HuAIITg mouse HDL. The concentration-dependent inhibition of CETP activity could be reproduced by the addition of delipidated HDL apolipoproteins from control mice, but it was abolished by a 1-h preheating treatment at 56 degrees C. In contrast, no significant inhibition of CETP activity was observed with the delipidated protein moiety of HuAITg HDL, and cholesteryl ester transfer rates remained unchanged before and after a 1-h, 56 degrees C preheating step. Finally, the CETP-mediated transfer of radiolabeled cholesteryl esters from human low density lipoprotein to human HDL was significantly higher in the presence of lipoprotein-deficient plasma from HuAITg mice than in the presence of lipoprotein-deficient plasma from control mice. Interestingly, cholesteryl ester transfer rates measured with both control and HuAITg lipoprotein-deficient plasmas became remarkably similar following a 1-h, 56 degrees C preheating treatment. It is concluded that human, control mouse, and HuAIITg mouse HDL contain a heat-labile lipid transfer inhibitory activity that is absent from HDL of HuAITg and HuAIAIITg mice. Alterations in CETP-lipoprotein binding did not account for differential lipid transfer inhibitory activities.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 015510160

Download citation: RISBibTeXText

PMID: 9305883

DOI: 10.1074/jbc.272.39.24287


Related references

Transfer of cholesteryl esters from high-density lipoproteins to beta-very low density lipoproteins in transgenic mice co-expressing Simian cholesteryl ester transfer protein and a human dysfunctional apolipoprotein E. Clinical Research 41(2): 213A, 1993

Remodelling of lipoproteins in transgenic mice expressing human cholesteryl ester transfer protein. Biochimica et Biophysica Acta 1255(3): 301-310, 1995

Transgenic mice expressing human Apo B and human cholesteryl ester transfer protein have a lipoprotein-cholesterol profile similar to that of normolipidemic humans. Circulation 90(4 PART 2): I134, 1994

Reduced high density lipoprotein cholesterol in human cholesteryl ester transfer protein transgenic mice. Journal of Biological Chemistry 266(17): 10796-10801, 1991

Human ApoA-II inhibits the hydrolysis of HDL triglyceride and the decrease of HDL size induced by hypertriglyceridemia and cholesteryl ester transfer protein in transgenic mice. Journal of Clinical Investigation 94(6): 2457-2467, 1994

Cholesteryl ester transfer protein activity enhances plasma cholesteryl ester formation. Studies in CETP transgenic mice and human genetic CETP deficiency. Arteriosclerosis, Thrombosis, and Vascular Biology 17(6): 1045-1052, 1997

An interaction between the human cholesteryl ester transfer protein (CETP) and apolipoprotein A-I genes in transgenic mice results in a profound CETP-mediated depression of high density lipoprotein cholesterol levels. Journal of Clinical Investigation 90(2): 505-510, 1992

Human plasma phospholipid transfer protein increases the antiatherogenic potential of high density lipoproteins in transgenic mice. Arteriosclerosis, Thrombosis, and Vascular Biology 20(4): 1082-1088, 2000

Thyroid hormone increases plasma cholesteryl ester transfer protein activity and plasma high-density lipoprotein removal rate in transgenic mice. Metabolism: Clinical and Experimental 50(5): 530-536, 2001

Cholesteryl ester transfer protein corrects dysfunctional high density lipoproteins and reduces aortic atherosclerosis in lecithin cholesterol acyltransferase transgenic mice. Journal of Biological Chemistry 274(52): 36912-36920, 1999

Decreased cholesteryl ester transfer protein (CETP) mRNA and protein and increased high density lipoprotein following lipopolysaccharide administration in human CETP transgenic mice. Journal of Clinical Investigation 95(4): 1587-1594, 1995

Ldl in human Apob transgenic mice fails to restore cholesteryl ester stores in Apoa-i-deficient mice. Circulation 96(8 SUPPL ): I4, 10/21/97, 1997

Human plasma cholesteryl ester transfer protein enhances the transfer of cholesteryl ester from high density lipoproteins into cultured HepG2 cells. Journal of Biological Chemistry 262(8): 3482-3487, 1987

Expression of human cholesteryl ester transfer protein cetp gene in transgenic mice. Circulation 82(4 SUPPL 3): III432, 1990

Apolipoprotein A-I metabolism in cholesteryl ester transfer protein transgenic mice. Insights into the mechanisms responsible for low plasma high density lipoprotein levels. Journal of Biological Chemistry 269(11): 8044-8051, 1994