期刊
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
卷 326, 期 2, 页码 395-405出版社
AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
DOI: 10.1124/jpet.107.134833
关键词
-
资金
- NCRR NIH HHS [G12RR003032, G12 RR003032] Funding Source: Medline
- NHLBI NIH HHS [K01 HL076623, K01HL076623] Funding Source: Medline
- NIEHS NIH HHS [R01 ES014472-01A1, R01 ES014472, R01ES014471] Funding Source: Medline
- NINDS NIH HHS [U54NS041071, U54 NS041071] Funding Source: Medline
We previously reported that apolipoprotein (Apo) E-deficient, ApoB48-containing (E-/B48) lipoproteins inhibited expression of lysosomal hydrolase and transformed mouse peritoneal macrophages (MPMs) into foam cells. The present study examined the effect of 2-aminopurine (2-AP), an inhibitor of eukaryotic initiation factor (eIF)-2 alpha phosphorylation, on E-/B48 lipoprotein-induced changes in gene expression and foam cell formation. Our data demonstrated that E-/B48 lipoproteins enhanced phosphorylation of eIF-2 alpha in macrophages. Incubation of MPMs with E-/B48 lipoproteins inhibited the translation efficiency of mRNAs encoding lysosomal acid lipase, cathepsin B, and cation-dependent mannose 6 phosphate receptor, with a parallel reduction in the level of these proteins. Addition of 2-AP to the culture media alleviated the suppressive effect of E-/B48 lipoproteins on lysosomal hydrolase mRNA translation, increased macrophage degradation of E-/B48 lipoproteins, and inhibited foam cell formation. Transfection of MPMs with a nonphosphorylatable eIF-2 alpha mutant also attenuated the suppressive effect of E-/B48 lipoproteins on expression of lysosomal acid lipase, associated with a reduced accumulation of cellular cholesterol esters. This is the first demonstration that ApoE-deficient lipoproteins inhibit lysosomal hydrolase synthesis and transform macrophages into foam cells through induction of eIF-2 alpha phosphorylation.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据