Biomaterial Database

Early steps in reverse cholesterol transport: cholesteryl ester hydrolase and other hydrolases. 2012

Shobha Ghosh

Division of Pulmonary and Critical Care, Department of Internal Medicine, VCU Medical Center, Richmond, Virginia 23298-0050, USA. shobha@vcu.edu

OBJECTIVE Several controversies exist related to the molecular identity and subcellular localization of the enzyme catalyzing macrophage cholesteryl ester hydrolysis. Some of these issues have been reviewed earlier and this review summarizes new developments that describe effects of overexpression or gene ablation. The main objective is to highlight the disagreement between lack of gene expression and incomplete abolition of macrophage cholesteryl ester hydrolytic activity and to emphasize the importance of redundancy. RESULTS New information resulting from the continuing characterization of the various cholesteryl ester hydrolases (hormone-sensitive lipase, HSL; cholesteryl ester hydrolase, CEH; and KIAA1363/NCEH1) is reviewed. Whereas CEH overexpression leads to beneficial effects such as decreased inflammation, improved glucose tolerance/insulin sensitivity, and attenuation of atherosclerotic lesion progression, deficiency/ablation of HSL or KIAA1363/NCEH1 results in incomplete loss of macrophage cholesteryl ester hydrolysis/turnover. New paradigms challenging the classical view of cytoplasmic cholesteryl ester hydrolysis and reverse cholesterol transport are also presented. CONCLUSIONS The observed beneficial effects of CEH overexpression identify macrophage cholesteryl ester hydrolysis as an important therapeutic target and future studies will determine whether similar effects are obtained with overexpression of HSL or KIAA1363/NCEH1. It is imperative that, for clinical benefit, mechanisms to enhance endogenous cholesteryl ester hydrolase(s) are established.

UI	MeSH Term	Description	Entries
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
D002788	Cholesterol Esters	Fatty acid esters of cholesterol which constitute about two-thirds of the cholesterol in the plasma. The accumulation of cholesterol esters in the arterial intima is a characteristic feature of atherosclerosis.	Cholesterol Ester,Cholesteryl Ester,Cholesteryl Esters,Ester, Cholesterol,Ester, Cholesteryl,Esters, Cholesterol,Esters, Cholesteryl
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D006867	Hydrolases	Any member of the class of enzymes that catalyze the cleavage of the substrate and the addition of water to the resulting molecules, e.g., ESTERASES, glycosidases (GLYCOSIDE HYDROLASES), lipases, NUCLEOTIDASES, peptidases (PEPTIDE HYDROLASES), and phosphatases (PHOSPHORIC MONOESTER HYDROLASES). EC 3.	Hydrolase
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
D001692	Biological Transport	The movement of materials (including biochemical substances and drugs) through a biological system at the cellular level. The transport can be across cell membranes and epithelial layers. It also can occur within intracellular compartments and extracellular compartments.	Transport, Biological,Biologic Transport,Transport, Biologic
D015971	Gene Expression Regulation, Enzymologic	Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.	Enzymologic Gene Expression Regulation,Regulation of Gene Expression, Enzymologic,Regulation, Gene Expression, Enzymologic
D050197	Atherosclerosis	A thickening and loss of elasticity of the walls of ARTERIES that occurs with formation of ATHEROSCLEROTIC PLAQUES within the ARTERIAL INTIMA.	Atherogenesis,Atherogeneses,Atheroscleroses
D051379	Mice	The common name for the genus Mus.	Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D018345	Mice, Knockout	Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.	Knockout Mice,Mice, Knock-out,Mouse, Knockout,Knock-out Mice,Knockout Mouse,Mice, Knock out