Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Stulnig, TM; Klocker, H; Harwood, HJ; Jürgens, G; Schönitzer, D; Jarosch, E; Huber, LA; Amberger, A; Wick, G.
In vivo LDL receptor and HMG-CoA reductase regulation in human lymphocytes and its alterations during aging.
Arterioscler Thromb Vasc Biol. 1995; 15(7):872-878
Doi: 10.1161/01.ATV.15.7.872
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- Co-Autor*innen der Med Uni Graz
- Jürgens Günther
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- 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 age significantly influences the transcriptional regulation of the LDL receptor in extrahepatic cells in vivo.
- Find related publications in this database (using NLM MeSH Indexing)
- Adult -
- Aged -
- Aging - blood
- Down-Regulation - blood
- Humans - blood
- Hydroxymethylglutaryl CoA Reductases - blood
- Lipoproteins, HDL - blood
- Lipoproteins, LDL - blood
- Lymphocytes - metabolism
- Polymerase Chain Reaction - metabolism
- RNA, Messenger - blood
- RNA-Directed DNA Polymerase - blood
- Receptors, LDL - metabolism
- Find related publications in this database (Keywords)
- Aging
- Hydroxymethylglutaryl Coenzyme a Reductase
- Transcriptional Regulation
- LDL Receptor
- HDL Receptor