Okazaki_2008_J.Biol.Chem_283_33357

Reference

Title : Identification of neutral cholesterol ester hydrolase, a key enzyme removing cholesterol from macrophages - Okazaki_2008_J.Biol.Chem_283_33357
Author(s) : Okazaki H , Igarashi M , Nishi M , Sekiya M , Tajima M , Takase S , Takanashi M , Ohta K , Tamura Y , Okazaki S , Yahagi N , Ohashi K , Amemiya-Kudo M , Nakagawa Y , Nagai R , Kadowaki T , Osuga J , Ishibashi S
Ref : Journal of Biological Chemistry , 283 :33357 , 2008
Abstract :

Unstable lipid-rich plaques in atherosclerosis are characterized by the accumulation of macrophage foam cells loaded with cholesterol ester (CE). Although hormone-sensitive lipase and cholesteryl ester hydrolase (CEH) have been proposed to mediate the hydrolysis of CE in macrophages, circumstantial evidence suggests the presence of other enzymes with neutral cholesterol ester hydrolase (nCEH) activity. Here we show that the murine orthologue of KIAA1363, designated as neutral cholesterol ester hydrolase (NCEH), is a microsomal nCEH with high expression in murine and human macrophages. The effect of various concentrations of NaCl on its nCEH activity resembles that on endogenous nCEH activity of macrophages. RNA silencing of NCEH decreases nCEH activity at least by 50%; conversely, its overexpression inhibits the CE formation in macrophages. Immunohistochemistry reveals that NCEH is expressed in macrophage foam cells in atherosclerotic lesions. These data indicate that NCEH is responsible for a major part of nCEH activity in macrophages and may be a potential therapeutic target for the prevention of atherosclerosis.

PubMedSearch : Okazaki_2008_J.Biol.Chem_283_33357
PubMedID: 18782767
Gene_locus related to this paper: human-NCEH1

Related information

Gene_locus human-NCEH1

Citations formats

Okazaki H, Igarashi M, Nishi M, Sekiya M, Tajima M, Takase S, Takanashi M, Ohta K, Tamura Y, Okazaki S, Yahagi N, Ohashi K, Amemiya-Kudo M, Nakagawa Y, Nagai R, Kadowaki T, Osuga J, Ishibashi S (2008)
Identification of neutral cholesterol ester hydrolase, a key enzyme removing cholesterol from macrophages
Journal of Biological Chemistry 283 :33357

Okazaki H, Igarashi M, Nishi M, Sekiya M, Tajima M, Takase S, Takanashi M, Ohta K, Tamura Y, Okazaki S, Yahagi N, Ohashi K, Amemiya-Kudo M, Nakagawa Y, Nagai R, Kadowaki T, Osuga J, Ishibashi S (2008)
Journal of Biological Chemistry 283 :33357