Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.3.1.21 (CPT)
 4,580 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of two cell-permeable cyclic AMP analogues, 8-chloro cyclic AMP (8-Cl cAMP) and 8-(4-chlorophenylthio) cyclic AMP (8-CPT cAMP), on cholesterol esterification, cholesteryl ester hydrolysis and bile acid synthesis were compared in cultured rat and hamster hepatocytes. Cholesterol esterification, as measured by the incorporation of [3H]oleate into cholesteryl ester, was increased by 58-88% by the analogues in rat hepatocytes and by 33-43% in hamster cells. The response in rat hepatocytes, however, was observed after a relatively short incubation time (28% increase after 1 hr), whereas that in hamster cells required a longer period (36% after 12 hr) to become apparent. The activity of the cytosolic neutral cholesteryl ester hydrolase in rat hepatocytes was also stimulated by both cyclic AMP analogues (31-37%, but the microsomal activity was unaffected. In hamster hepatocytes, however, microsomal cholesteryl ester hydrolase activity was increased (47-80%) in the presence of 8-Cl cAMP or 8-CPT cAMP. Bile acid synthesis was increased by 8-CPT cyclic AMP in rat cells (approximately 25%) but was unchanged by both analogues in hamster hepatocytes. These results indicate significant differences in the way in which cholesterol metabolism responds to cyclic AMP in cultured rat and hamster hepatocytes.
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PMID:Comparison of the effects of cyclic AMP analogues on cholesterol metabolism in cultured rat and hamster hepatocytes. 893 53

Peroxisome proliferator-activated receptors (PPARs) are key regulators of macrophage lipid metabolism. We compared the effects of three PPAR activators (bezafibrate, fenofibrate, and troglitazone) on the mRNA levels of genes involved in lipid metabolism in primary human macrophages and macrophage-derived foam cells. Treatment of human macrophages for 24 hours with 100 micro mol/L bezafibrate, a nonselective drug that activates the 3 PPAR subtypes (PPARalpha, PPARbeta/delta, and PPARgamma), caused an 87% (P <.01) and a 230% rise in CD36 and adipocyte fatty acid-binding protein (aP2) mRNA levels, respectively, whereas the expressions of PPARgamma, PPARalpha, acyl-CoA oxidase, carnitine palmitoyltransferase I (CPT-I), adenosine triphosphate (ATP)-binding cassette transporter 1 (ABCA1), neutral cholesteryl ester hydrolase, and lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) were not modified. However, treatment with selective PPARalpha (fenofibrate at 100 micro mol/L) and PPARgamma (troglitazone at 5 micro mol/L) activators had different effects. Fenofibrate increased PPARalpha (62%, P <.05) and LOX-1 (180%, P <.05) mRNA levels; and troglitazone upregulated CPT-I expression (75%, P <.05). When the effects of these drugs were assessed in macrophage-derived foam cells, we found that troglitazone caused a 134% (P <.05) and a 66% (P <.01) rise in ABCA1 and CPT-I mRNA levels, respectively, whereas the 3 drugs significantly increased aP2 transcripts (about 100% induction). Given that troglitazone treatment resulted in the upregulation of genes involved in the mitochondrial beta-oxidation of fatty acids (CPT-I) and in the reverse-cholesterol-transport pathway (ABCA1), we subsequently determined whether these changes affected intracellular cholesterol ester accumulation. In macrophage-derived foam cells a significant reduction (32%, P <.01) was observed in intracellular cholesterol accumulation after troglitazone, but not after bezafibrate or fenofibrate treatment. Since CPT-I inhibition promotes cholesterol incorporation into cholesteryl esters in macrophages, study is now needed on whether CPT-I induction by troglitazone may reduce the availability of fatty acids for synthesizing cholesterol esters, leading to less foam cell formation.
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PMID:Differential effects of peroxisome proliferator-activated receptor activators on the mRNA levels of genes involved in lipid metabolism in primary human monocyte-derived macrophages. 1275