Inhibition of cholesterylester accumulation by 17β-estradiol in macrophages through activation of neutral cholesterol esterase
1996; Elsevier BV; Volume: 1300; Issue: 3 Linguagem: Inglês
10.1016/0005-2760(96)00009-4
ISSN1879-145X
AutoresTakako Tomita, Fusae Sawamura, Reiko Uetsuka, Tsuyoshi Chiba, Shinji Miura, Masahiko Ikeda, Isao Tomita,
Tópico(s)Lipoproteins and Cardiovascular Health
ResumoPremenopausal women are at a lower risk of coronary heart diseases relative to age matched men. However, the underlying mechanisms are not clearly understood. This article studies the effects of 17β-estradiol (17β-E2) at physiological concentrations on the cholesterylester metabolism in macrophages (J774 A.1 cells) with a particular focus on neutral cholesterol esterase (N-CEase). Cells were incubated with β-VLDL, [1-14C]oleic acid and 17β-E2 (0.25 and 2.5 nM). 17β-E2 dose-dependently reduced cholesteryl-[1-14C]oleate (14C-CO) at 36 h and 48 h relative to the control. It also stimulated hydrolysis of 14C-CO in foam cells on 36 h and 48 h incubation. In addition, 17β-E2 markedly increased N-CEase activity at 24 h and 36 h. This increase preceded the enhanced hydrolysis of cholesterylester. 17α-E2 (inactive isomer), estrone and estriol had no stimulatory action on N-CEase, whereas progesterone and testosterone inhibited it. 17β-E2-treatment (24 h) increased the activity of cyclic AMP-dependent protein kinase (A-kinase). DEAE-cellulose column chromatography revealed that an isoform (type II) of A-kinase appeared in 17β-E2-treated cells in addition to type I of A-kinase found in the control cells. These results suggest that inhibition of cholesterylester accumulation in macrophages by 17β-E2 is mediated by an enhancement of N-CEase activity possibly through an increase in A-kinase.
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