Regulation of hepatic neutral cholesteryl ester hydrolase by hormones and changes in cholesterol flux. 1998

S Ghosh, and R Natarajan, and W M Pandak, and P B Hylemon, and W M Grogan
Department of Biochemistry, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298, USA.

To understand molecular events in regulation of hepatic neutral cholesteryl ester hydrolase (EC3.1.1.13; CEH), catalytic activity, protein mass, and mRNA levels were measured in rats with various perturbations of hepatic cholesterol metabolism. Cholesterol feeding decreased activity (56 +/- 2%), mass (44 +/- 2%), and mRNA (14 +/- 3%). The cholesterol precursor mevalonate also decreased activity (42 +/- 6%), mass (76 +/- 3%), and mRNA (23 +/- 16%). Inhibition of cholesterol biosynthesis by lovastatin increased activity (65 +/- 12%) and mRNA (31 +/- 24%). Stimulation of cholesterol efflux by chronic biliary diversion increased activity (138 +/- 34%), mass (29 +/- 7%), and mRNA (146 +/- 28%). Chenodeoxycholate feeding decreased activity (46 +/- 6%) and mRNA (26 +/- 12%). These data suggest rational regulation of CEH in response to changes in cholesterol flux through the liver. In primary hepatocytes, steady-state mRNA markedly decreased during 72-h cultures and addition of L-thyroxine and dexamethasone synergistically maintained mRNA levels near control values. Lovastatin increased mRNA levels by 103 +/- 15%. Taurocholate and phorbol 12-myristate 13-acetate suppressed mRNA (61 +/- 4% and 49 +/- 13%, respectively), suggesting that protein kinase C mediated effects of bile acids on CEH mRNA levels. These data suggest regulation of CEH by hormones and signal transduction in addition to changes in cholesterol flux.

UI MeSH Term Description Entries
D007425 Intracellular Membranes Thin structures that encapsulate subcellular structures or ORGANELLES in EUKARYOTIC CELLS. They include a variety of membranes associated with the CELL NUCLEUS; the MITOCHONDRIA; the GOLGI APPARATUS; the ENDOPLASMIC RETICULUM; LYSOSOMES; PLASTIDS; and VACUOLES. Membranes, Intracellular,Intracellular Membrane,Membrane, Intracellular
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D008297 Male Males
D002784 Cholesterol The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. Epicholesterol
D002787 Sterol Esterase An enzyme that catalyzes the hydrolysis of CHOLESTEROL ESTERS and some other sterol esters, to liberate cholesterol plus a fatty acid anion. Cholesterol Esterase,15-Ketosteryl Oleate Hydrolase,Acylcholesterol Lipase,Cholesterol Ester Hydrolase,Cholesteryl Oleate Hydrolase,Cholesterylester Hydrolase,Hormone-Sensitive Lipase,Lipase A (Lysosomal Acid Cholesterol Esterase),Lipoidal Steroid Esterase,Lysosomal Acid Cholesterol Esterase,Lysosomal Acid Lipase,Steroid Hormone Esterase,Sterol Ester Acylhydrolase,15 Ketosteryl Oleate Hydrolase,Acid Lipase, Lysosomal,Acylhydrolase, Sterol Ester,Esterase, Cholesterol,Esterase, Lipoidal Steroid,Esterase, Steroid Hormone,Esterase, Sterol,Hormone Sensitive Lipase,Hydrolase, 15-Ketosteryl Oleate,Hydrolase, Cholesterol Ester,Hydrolase, Cholesteryl Oleate,Hydrolase, Cholesterylester,Lipase, Acylcholesterol,Lipase, Hormone-Sensitive,Steroid Esterase, Lipoidal
D003907 Dexamethasone An anti-inflammatory 9-fluoro-glucocorticoid. Hexadecadrol,Decaject,Decaject-L.A.,Decameth,Decaspray,Dexasone,Dexpak,Hexadrol,Maxidex,Methylfluorprednisolone,Millicorten,Oradexon,Decaject L.A.
D004032 Diet Regular course of eating and drinking adopted by a person or animal. Diets
D005938 Glucocorticoids A group of CORTICOSTEROIDS that affect carbohydrate metabolism (GLUCONEOGENESIS, liver glycogen deposition, elevation of BLOOD SUGAR), inhibit ADRENOCORTICOTROPIC HORMONE secretion, and possess pronounced anti-inflammatory activity. They also play a role in fat and protein metabolism, maintenance of arterial blood pressure, alteration of the connective tissue response to injury, reduction in the number of circulating lymphocytes, and functioning of the central nervous system. Glucocorticoid,Glucocorticoid Effect,Glucorticoid Effects,Effect, Glucocorticoid,Effects, Glucorticoid
D006728 Hormones Chemical substances having a specific regulatory effect on the activity of a certain organ or organs. The term was originally applied to substances secreted by various ENDOCRINE GLANDS and transported in the bloodstream to the target organs. It is sometimes extended to include those substances that are not produced by the endocrine glands but that have similar effects. Hormone,Hormone Receptor Agonists,Agonists, Hormone Receptor,Receptor Agonists, Hormone
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

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