Oxidized LDL attenuates apoptosis in monocytic cells by activating ERK signaling

被引：32

作者：

Namgaladze, Dmitry ^{[1
]}

Kollas, Andreas ^{[1
]}

Bruene, Bernhard ^{[1
]}

机构：

[1] Goethe Univ Frankfurt, Fac Med, Inst Biochem 1, D-60590 Frankfurt, Germany

来源：

JOURNAL OF LIPID RESEARCH | 2008年 / 49卷 / 01期

关键词：

atherosclerosis; oxidized low density lipoprotein; reactive oxygen species; extracellular signal-regulated kinase;

D O I：

10.1194/jlr.M700100-JLR200

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Low concentrations of oxidized low density lipoprotein ( OxLDL) are cytoprotective for phagocytes, although the underlying mechanisms remain unclear. We investigated signaling pathways used by OxLDL to attenuate apoptosis in monocytic cells. OxLDL at 25-50 mu g/ml inhibited staurosporine-induced apoptosis in THP-1 cells and mouse peritoneal macrophages, and it was cytoprotective in human primary monocytes upon serum withdrawal. Attenuated cell demise was reversed by blocking extracellular signal-regulated kinase (ERK) signaling. Translocation of cytochrome c to the cytosol was attenuated by OxLDL, which again demanded ERK signaling. Analysis of Bcl-2 family proteins revealed phosphorylation of Bad at serine 112 as well as ERK-dependent inhibition of Mcl-1 degradation. Although the formation of reactive oxygen species (ROS) is an established signal generated by OxLDL, ROS scavengers did not interfere with cell protection by OxLDL.

引用

收藏

页码：58 / 65

页数：8

相关论文

共 32 条

[11] Granulocyte macrophage colony-stimulating factor signaling and proteasome inhibition delay neutrophil apoptosis by increasing the stability of Mcl-1 [J].

Derouet, M ;

Thomas, L ;

Cross, A ;

Moots, RJ ;

Edwards, SW .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (26) :26915-26921

[12] Oxidants inhibit ERK/MAPK and prevent its ability to delay neutrophil apoptosis downstream of mitochondrial changes and at the level of XIAP [J].

Gardai, SJ ;

Whitlock, BB ;

Xiao, YQ ;

Bratton, DB ;

Henson, PM .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (43) :44695-44703

[13] Free radicals, mitochondria, and oxidized lipids - The emerging role in signal transduction in vascular cells [J].

Gutierrez, Jessica ;

Ballinger, Scott W. ;

Darley-Usmar, Victor M. ;

Landar, Aimee .

CIRCULATION RESEARCH, 2006, 99 (09) :924-932

[14] Oxidized LDL can promote human monocyte survival [J].

Hamilton, JA ;

Whitty, G ;

Jessup, W .

ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2000, 20 (10) :2329-2331

[15] Comparison of macrophage responses to oxidized low-density lipoprotein and macrophage colony-stimulating factor (M-CSF or CSF-1) [J].

Hamilton, JA ;

Byrne, R ;

Jessup, W ;

Kanagasundaram, V ;

Whitty, G .

BIOCHEMICAL JOURNAL, 2001, 354 :179-187

[16] Oxidized low density lipoprotein inhibits macrophage apoptosis by blocking ceramide generation, thereby maintaining protein kinase B activation and Bcl-XL levels [J].

Hundal, RS ;

Gómez-Muñoz, A ;

Kong, JY ;

Salh, BS ;

Marotta, A ;

Duronio, V ;

Steinbrecher, UP .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (27) :24399-24408

[17]

Hundal RS, 2001, J LIPID RES, V42, P1483

[18] 1-methyl-4-phenylpyridinium induces autocrine excitotoxicity, protease activation, and neuronal apoptosis [J].

Leist, M ;

Volbracht, C ;

Fava, E ;

Nicotera, P .

MOLECULAR PHARMACOLOGY, 1998, 54 (05) :789-801

[19] Activation of the ERK1/2 signaling pathway promotes phosphorylation and proteasome-dependent degradation of the BH3-only protein, Bim [J].

Ley, R ;

Balmanno, K ;

Hadfield, K ;

Weston, C ;

Cook, SJ .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (21) :18811-18816

[20] Reduced macrophage apoptosis is associated with accelerated atherosclerosis in low-density lipoprotein receptor-null mice [J].

Liu, J ;

Thewke, DP ;

Su, YR ;

Linton, MF ;

Fazio, S ;

Sinensky, MS .

ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2005, 25 (01) :174-179

← 1 2 3 4 →