Lipid peroxidation proteins

Chemicals produce adverse effects in the developing embryo and fetus by a variety of mechanisms (Bishop Kimmel, 1997). These may involve interactions of the exogenous agent with endogenous receptors, adduction of reactive intermediates to DNA or proteins, lipid peroxidation, enzyme inhibition, cell membrane alterations and others (US NRC, 2000). 

Peroxides - The destruction of cytochrome P-450 during lipid peroxidation is generally assumed to result from nonspecific degradation of microsomal proteins. Lipid peroxidation indeed causes general protein damage and thus falls outside the scope of this review. Evidence nevertheless exists that lipid peroxides can inactivate cytochrome P-450 enzymes with some specificity (a) lipids extracted from peroxidized microsomes destroy the cytochrome P-450 complement of fresh microsomes, (b) linoleic acid hydroperoxide causes equimolar, concentration-dependent, loss of microsomal cytochrome P-450 and heme, and (c) cytochrome b5 and cytochrome P-450 reductase are not affected except by relatively high concentrations of linoleic acid hydroperoxide. 

Although MDA, an end-product of the lipid peroxidation process is thought to be the major contributor to the chromogen, it has now become clear that a number of other species such as sucrose, urea, proteins and other aldehydes also react with TBA to produce chromogens that absorb at a wavelength near to 532 nm (Marshall et al., 1985). Moreover, it should also be noted that since only a small proportion (1-2%) of the lipid peroxidation... 

However, peroxidation can also occur in extracellular lipid transport proteins, such as low-density lipoprotein (LDL), that are protected from oxidation only by antioxidants present in the lipoprotein itself or the exttacellular environment of the artery wall. It appeats that these antioxidants are not always adequate to protect LDL from oxidation in vivo, and extensive lipid peroxidation can occur in the artery wall and contribute to the pathogenesis of atherosclerosis (Palinski et al., 1989 Ester-bauer et al., 1990, 1993 Yla-Herttuala et al., 1990 Salonen et al., 1992). Once initiation occurs the formation of the peroxyl radical results in a chain reaction, which, in effect, greatly amplifies the severity of the initial oxidative insult. In this situation it is likely that the peroxidation reaction can proceed unchecked resulting in the formation of toxic lipid decomposition products such as aldehydes and the F2 isoprostanes (Esterbauer et al., 1991 Morrow et al., 1990). In support of this hypothesis, cytotoxic aldehydes such as 4-... 

In contrast to MDA and hydroxynonenai, other aldehyde products of lipid peroxidation are hydrophobic and remain closely associated with LDL to accumulate to mil-limolar concentrations. Aldehydes at these elevated levels react with the protein portion of the LDL molecule, apolipoprotein B (apoB). Accumulated aldehydes bind the free amino groups from lysine residues in addition to other functional groups (-OH, -SH) on the apoB polypeptide. Consequently, the protein takes on a net negative charge and complete structural rearrangement results in the formation of ox-LDL. ox-LDL is no longer recognized by the LDL receptor, and has several pro-inflammatory properties (discussed below). 

Copper salts such as CuS04 are potent catalysts of the oxidative modification of LDL in vitro (Esterbauer et al., 1990), although more than 95% of the copper in human serum is bound to caeruloplasmin. Cp is an acute-phase protein and a potent inhibitor of lipid peroxidation, but is susceptible to both proteolytic and oxidative attack with the consequent release of catalytic copper ions capable of inducing lipid peroxidation (Winyard and... 

Primary and secondary products, and end-products of lipid peroxidation have all been shown to accumulate in senile cataracts (Babizhayev, 1989b Simonelli et al., 1989). Accumulation of these compounds in the lenticular epithelial membranes is a possible cause of damage preceding cataract formation. In senile cataracts there is also extensive oxidation of protein methionine and cysteine in both the membrane and cytosol components (Garner and Spector, 1980), while in aged normal lenses a lesser extent of oxidation was confined to the membrane. The authors therefore suggested that oxidation of membrane components was a precataract state. 

Peters, S.W., Jones, B.M., Jacobs, A. and Wagstaff, M. (1985). Free iron and lipid peroxidation in the plasma of patients with iron overload. In Proteins of Iron Storage and Transport (eds. G. Spik, J. Montreuil, R.R. Crichton and J. Mazurier) pp. 321-324. Elsevier Science Publishers, New York. 

Exposure of protein amino groups to MDA (formed by the degradation of lipid peroxides) or to oxygen radicals directly, generated by transition metals and hydrogen peroxide, induce fluorescence indistinguishable from that attributed to Amadori-adduct formation (Chio and Tappel, 1969), and leads to the formation of cross-links (Lunec a al., 1985). 

Several studies have demonstrated that treatment of diabetic patients with the sulphonylurea, gliclazide, is associated with a fall in lipid peroxidation, protein fluorescence and beneficial effects on platelet function (Florkowski et al., 1988 Jennings et al., 1992). These changes were seen to be independent of changes in giycaemic control. 

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