Increased gene expression of liver SREBP-2 in experimental chronic renal failure
| Autor: | Julian Swierczynski, Bolesław Rutkowski, E Kossowska, Elzbieta Sucajtys-Szulc, Wojciech Boguslawski, Michał Chmielewski |
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| Rok vydání: | 2005 |
| Předmět: |
Male
endocrine system medicine.medical_specialty Hypercholesterolemia Gene Expression Reductase Nephrectomy Internal medicine Gene expression medicine Transcriptional regulation Animals RNA Messenger Rats Wistar biology Sterol Sterol regulatory element-binding protein Rats Up-Regulation Disease Models Animal Endocrinology Cholesterol Liver Receptors LDL Enzyme Induction LDL receptor HMG-CoA reductase biology.protein Kidney Failure Chronic lipids (amino acids peptides and proteins) Hydroxymethylglutaryl CoA Reductases Cardiology and Cardiovascular Medicine Homeostasis Sterol Regulatory Element Binding Protein 2 |
| Zdroj: | Atherosclerosis. 191(2) |
| ISSN: | 0021-9150 |
| Popis: | Sterol regulatory element-binding protein-2 (SREBP-2) is a transcription factor regarded as the main regulator of cholesterol homeostasis. Therefore, increased level of SREBP-2 could be responsible for hypercholesterolemia, which is observed in experimental chronic renal failure (CRF). This study was designed primary to evaluate the impact of experimental CRF (5/6 nephrectomy model) on rat liver SREBP-2 gene expression. In CRF rats, a twofold increase in SREBP-2 mRNA level, as well as in mature SREBP-2 protein abundance was found, when compared to control animals. It was associated with enhanced activity and mRNA abundance of liver HMG-CoA reductase, a rate-limiting enzyme for cholesterol biosynthesis. A twofold increase in liver cholesterologenesis rate was also noted. We conclude that experimental CRF is associated with increased liver SREBP-2 gene expression. This is probably the cause for enhanced HMG-CoA reductase gene expression and, consequently, for increase in liver cholesterol synthesis in CRF rats. Despite increased SREBP-2 gene expression we found LDL-receptor mRNA level to be lower than in controls, suggesting SREBP-2 independent mechanisms of LDL-receptor transcriptional regulation in CRF rats. Enhanced cholesterol synthesis and decreased LDL-receptor mRNA level are probably responsible for an almost fourfold increase in serum cholesterol concentration in CRF rats. |
| Databáze: | OpenAIRE |
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