Oxidized lipids, biological effects

In summary, the binding of oxLDL and/or lipids to several SC receptors (SRAI/II, CD36, CD68) has been clearly demonstrated. Most of other receptors may potentially bind oxLDL or lipids. Consequently, the cellular internalization of oxidized lipids by the SC receptor pathways may be involved in the biological effect of oxLDL, such as apoptosis induction. As a likely major ligand and because of their oxidized lipid contents, oxLDL may have many putative effects on different cells, such as alteration of cell signaling and gene expression. 

HDL HDL promote the cholesterol efflux from arterial. In addition, HDL protect LDL from oxidation and induction of subsequent cytotoxicity (Von Eckardstein et al., 2001 Kwiterovich, 1998 Berliner and Heinecke, 1996). This effect is apparently due to the presence of 2 enzymes (paraoxonase and PAF-acetylhydrolase bound to HDL) which may hydrolyse the oxidized lipids of LDL, thus blocking the subsequent biological responses (Hajjar and Haberland, 1997). Moreover, HDL could reduce hydroperoxides to their corresponding hydroxides, or extract oxidized lipids from oxidized LDL (Bonnefont-Rousselot et al., 1999). HDL inhibit oxidized LDL cytotoxicity (Hessler et al., 1979), through inhibition of oxT, DT. -induced stress and calcium rise. HDL act as an anti-oxidant lowering the oxidative modification of LDL, and preventing the cells of arterial wall from the deleterious effect of oxidized LDL, but their precise cellular mechanism of protection still remains unknown. 

It has already been emphasized that apoptotic cells can be both, the source of oxidized phospholipids as well as the initiators of apoptosis. Oxidation of (poly)-unsaturated phospholipids leads to a large variety of oxidation products (see Chapter 1 and (Fruhwirth et al., 2007)). These compounds may have very different chemical structures. It can be anticipated that they exert very different physical effects in membranes and undergo specific interactions with their target proteins and lipids. As a consequence, the great variety of oxidized phospholipids should be reflected by a corresponding diversity of biological effects. In many studies investigating cell survival and/or cell death, the effects of oxidized lipid... 

Negre-Salvayre A, Alomar Y, Troly M, Salvayre R. Ultraviolet-treated lipoproteins as a model sy stem for the study of the biological effects of lipid peroxides on cultured cells. III. The protective effect of antioxidants (probucol, catechin, vitamin E) against the cytotoxicity of oxidized LDL occurs in two different ways. Biochim Biophy Acta 1991 1096 291-300. 

Logani, K.M. and Davis, R.E., Lipid oxidation Biological effects and antioxidants. Lipids, 12,485, 1980. 

It should not be assumed that hydroxy fatty acids are biologically inactive. Hydroxy fatty acids are chemotactic and vasoactive. Such fatty acids could perturb phospholipids in membranes. For instance, cardiolipin containing hydroxy-linoleic acid does not support the electron transport coupled to ATP production of the mitochondrion. 5-Hydroxy de-canoic acid is a well-known inhibitor of the K -ATP channel. Isoprostanes, trihydroxy oxidation products of arachi-donic acid, are vasoconstrictors (76). 13-Hydroxy linoleic acid (13-HODE) is a lipoxygenase-derived metabolite that influences the thromboresistant properties of endothelial cells in culture (77). However, there is some doubt about the tme nature of these hydroxy-fatty acids generated by the cells, as there are several GSH- and NADPH-dependent pathways that can immediately reduce hydroperoxy- to hydroxy-fatty acids. Furthermore, the reduction step of the analytical method would have converted the hydroperoxy- to a hydroxy-group. Nevertheless, much work remains to be done to determine the relative contribution of hydroperoxy- and hydroxy- to the biological effects of fried fat, and in particular their role in endothelial dysfunction and activation of factor VII. There have been earlier suggestions that a diet rich in lipid peroxidation products may lead to atherosclerosis and CHD (34,78). 

FIGURE 1.3 The diversity of biological effects of oxidatively modified lipids. A generalized scheme showing both the beneficial and deleterious effects that oxidized lipids can have overall, including the effects of oxidized phospholipids, oxidized FAs, oxysterols, haloge-nated phospholipids, and nitrated lipids. It should be remembered that not all oxidized lipids have these effects and indeed different individual oxidized species may have opposing effects. 

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