PMID: 7541292Jul 1, 1995Paper

In vivo LDL receptor and HMG-CoA reductase regulation in human lymphocytes and its alterations during aging

Arteriosclerosis, Thrombosis, and Vascular Biology
T StulnigG Wick

Abstract

The LDL receptor and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase play primary roles in the regulation of cellular cholesterol metabolism. To investigate the transcriptional regulation of lipid metabolism under physiological conditions ex vivo and its alterations during aging, we analyzed both the activity and mRNA concentration of the LDL receptor and HMG-CoA reductase in freshly isolated lymphocytes from healthy young and elderly donors. Data from fluorescent reverse transcriptase-polymerase chain reaction indicated that not only plasma LDL but also plasma HDL downregulates lymphocyte LDL receptor mRNA. Downregulation by HDL was three times more effective than that by LDL and presumably involved specific HDL binding sites. There was coordinate regulation of HMG-CoA reductase mRNA with LDL receptor mRNA that was independent of plasma lipoprotein concentrations. Despite elevated plasma concentrations of LDL, lymphocytes from elderly donors paradoxically expressed increased levels of the LDL receptor (P = .030) and HMG-CoA reductase mRNA (P = .062). The age-related dysregulation of the LDL receptor was predominantly due to impaired downregulation by plasma LDL rather than by HDL. Thus, not only LDL but also HDL and ...Continue Reading

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Citations

Jul 11, 2006·Wiener medizinische Wochenschrift·Dietmar Herndler-BrandstetterBeatrix Grubeck-Loebenstein
Dec 17, 1997·Clinical Biochemistry·H NägeleW Zeller
Jul 1, 1997·Experimental Gerontology·G Wick, B Grubeck-Loebenstein
May 19, 2000·Experimental Gerontology·L Robert
Jul 20, 2002·Clinical Pharmacokinetics·Fatemeh Akhlaghi, Andrew K Trull
Mar 17, 2010·Zhong xi yi jie he xue bao = Journal of Chinese integrative medicine·Jin JinQiu-li Zhou
Mar 2, 1999·Therapeutic Drug Monitoring·F AkhlaghiK Brown
Apr 27, 2000·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·T M StulnigW Waldhäusl
Nov 29, 2005·Metabolism: Clinical and Experimental·Gianluca RuiuMaurizio Cassader

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