Oxidized LDL attenuates apoptosis in monocytic cells by activating ERK signaling

Abstract

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 mg/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. Thus, activation of the ERK signaling pathway by OxLDL is important to protect phagocytes from apoptosis.-Namgaladze, D., A. Kollas, and B. Brü ne. Oxidized LDL attenuates apoptosis in monocytic cells by activating ERK signaling. J. Lipid Res. 2008. 49: 58-65.

Reactive Oxygen Species Mediate Oxidized Low-Density Lipoprotein-Induced Inhibition of Oct-4 Expression and Endothelial Differentiation of Bone Marrow Stem Cells

“…Ox-LDL promotes proliferation of macrophages and vascular smooth muscle cells, and inhibits apoptosis of macrophages and monocytes (16,20,22,31,32,41,58). On the other hand, ox-LDL inhibits proliferation and promotes apoptosis of vascular endothelial cells and EPCs (5,7,55).…”

Glucose Metabolism Is Required for Oxidized LDL–Induced Macrophage Survival

“…The apparent involvement of MEK1/2 in oxLDLinduced survival in this study and a previous study from our laboratory 7 contrasts with the study by Hundal and colleagues 38 but is supported by a study in THP-1 monocytes where oxLDL-induced survival required MEK1/2. 39 The disparity between our study and Hundal's study may be a result of survival measurement methods (ie, cell number versus MTT assay).…”

Attenuated suppression of the oxidative burst by cells dying in the presence of oxidized low density lipoprotein

“…In mouse peritoneal macrophages, oxLDL initiates an apoptotic program ( 18,27,28 ), while human macrophages die by necrosis ( 29 ). Moreover, pro-survival effects of oxLDL were also observed, with the notion that the degree of LDL oxidation appears important in balancing pro-versus antiapoptotic responses ( 19,28 ). Under the conditions used here, oxLDL induced a mixed type of cell death based on PS exposure, plasma membrane permeabilization, or caspase-3 activation.…”