Endotoxin, TNF, and IL-1 decrease cholesterol 7 alpha-hydroxylase mRNA levels and activity
Autor: | Allan S. Pollock, Kenneth R. Feingold, A H Moser, Carl Grunfeld, D K Spady |
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Jazyk: | angličtina |
Rok vydání: | 1996 |
Předmět: |
medicine.medical_specialty
endocrine system diseases Cholesterol medicine.drug_class Colestipol Acute-phase protein nutritional and metabolic diseases Lipid metabolism Cell Biology QD415-436 Cholesterol 7 alpha-hydroxylase urologic and male genital diseases Biochemistry chemistry.chemical_compound Endocrinology chemistry Bile acid sequestrant Internal medicine medicine Tumor necrosis factor alpha lipids (amino acids peptides and proteins) Lipoprotein medicine.drug |
Zdroj: | Journal of Lipid Research, Vol 37, Iss 2, Pp 223-228 (1996) |
ISSN: | 0022-2275 |
Popis: | Endotoxin (LPS) and cytokines increase cholesterol synthesis and the secretion of lipoproteins by the liver in rodents resulting in hypercholesterolemia. Cholesterol 7 alpha-hydroxylase (CAH) is the rate-limiting enzyme in the conversion of cholesterol to bile acids in the liver, the major regulated pathway by which cholesterol is eliminated from the body. Decreases in CAH would increase the quantity of cholesterol available for lipoprotein production. In the present study, we demonstrate that LPS, TNF, or IL-1 administration to Syrian hamsters produces a marked decrease in the levels of CAH mRNA in the liver. This marked decrease occurred even when the basal level of CAH expression was increased by feeding the bile acid sequestrant, colestipol. Additionally, a marked decrease was also observed when the animals were fed a cholesterol-enriched diet. Moreover, the decrease in CAH mRNA occurred very rapidly (decreased 66% by 90 min after LPS administration) and required relatively small doses of LPS (100 ng/100 g body weight). Lastly, the decrease in mRNA levels was accompanied by a decrease in CAH activity. This decrease in CAH could contribute to the increase in hepatic lipoprotein production induced by LPS and cytokines. CAH can be added to the growing list of proteins that regulate lipid metabolism and that are altered during the acute phase response. |
Databáze: | OpenAIRE |
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