The effect of calcium on phospholipid peroxidation

The effect of calcium ions on the peroxidation of ox-brain phospholipid liposomes in different free-radical catalysing systems has been assessed. Using thiobarbituric acid-reactivity (TBA) as a measure of lipid peroxidation, calcium ions both inhibited and enhanced peroxidation in the different systems.Changing the composition of the ox-brain phospholipid liposome with synthetic non TBA-reactive phosphatidylcholine, significantly altered its susceptibility to peroxidation both in the presence and absence of calcium ions.The results are discussed with reference to the possibility that calcium ions induce conformational changes in membrane phospholipids. Susceptibility to peroxidation is then influenced by a complex interrelationship between the qualitative lipid composition of the membrane, the pro-oxidant catalyst and the presence of calcium or other active ions.     

Rabbit liver microsomal lipid peroxidation. The effect of lipid on the rate of peroxidation

Rat and rabbit liver microsomes catalyze an NADPH-cytochrome P-450 reductase-dependent peroxidation of endogenous lipid in the presence of the chelate, ADP-Fe3+. Although liver microsomes from both species contain comparable levels of NADPH-cytochrome P-450 reductase and cytochrome P-450, the rate of lipid peroxidation (assayed by malondialdehyde and lipid hydroperoxide formation) catalyzed by rabbit liver microsomes is only about 40% of that catalyzed by rat liver microsomes. Microsomal lipid peroxidation was reconstituted with liposomes made from extracted microsomal lipid and purified protease-solubilized NADPH-cytochrome P-450 reductase from both rat and rabbit liver microsomes. The results demonstrated that the lower rates of lipid peroxidation catalyzed by rabbit liver microsomes could not be attributed to the specific activity of the reductase. Microsomal lipid from rabbit liver was found to be much less susceptible to lipid peroxidation. This was due to the lower polyunsaturated fatty acid content rather than the presence of antioxidants in rabbit liver microsomal lipid. Gas-liquid chromatographic analysis of fatty acids lost during microsomal lipid peroxidation revealed that the degree of fatty acid unsaturation correlated well with rates of lipid peroxidation.     

Selective and biphasic effect of the membrane lipid peroxidation product 4-hydroxy-2,3-nonenal on N-methyl-D-aspartate channels

Increased oxyradical production and membrane lipid peroxidation occur in neurons under physiological conditions and in neurodegenerative disorders. Lipid peroxidation can alter synaptic plasticity and may increase the vulnerability of neurons to excitotoxicity, but the underlying mechanisms are unknown. We report that 4-hydroxy-2,3-nonenal (4HN), an aldehyde product of lipid peroxidation, exerts a biphasic effect on NMDA-induced current in cultured rat hippocampal neurons with current being increased during the first 2 h and decreased after 6 h. Similarly, 4HN causes an early increase and a delayed decrease in NMDA-induced elevation of intracellular Ca2+ levels. In contrast, 4HN affects neither the ion current nor the Ca2+ response to alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA). The initial enhancement of NMDA-induced current is associated with increased phosphorylation of the NR1 receptor subunit, whereas the delayed suppression of current is associated with cellular ATP depletion and mitochondrial membrane depolarization. Cell death induced by 4HN is attenuated by an NMDA receptor antagonist, but not by an AMPA receptor antagonist. A secreted form of amyloid precursor protein, previously shown to protect neurons against oxidative and excitotoxic insults, prevented each of the effects of 4HN including the early and late changes in NMDA current, delayed ATP depletion, and cell death. These findings show that the membrane lipid peroxidation product 4HN can modulate NMDA channel activity, suggesting a role for this aldehyde in physiological and pathophysiological responses of neurons to oxidative stress.     

The inhibitory effect of succinate on radiation-enhanced mitochondrial lipid peroxidation

The degree of mitochondrial ADP/Fe/NADPH-induced lipid peroxidation was increased up to the fourth day after 9.0 Gy whole body gamma-irradiation. The lipid peroxidation inhibiting effect of succinate added to isolated mitochondria was diminished as a consequence of irradiation. The succinate, administered in vivo prior to irradiation, decreased the amount of malondialdehyde production and protected the succinate dehydrogenase enzyme against inactivation. The mean survival of succinate-pretreated animals was much longer than that of controls. The role of mitochondrial lipid peroxidation in the pathogenesis of radiation injury is discussed.     

Effect of calcium on lipid peroxidation in plasma membranes]

Process of nonenzymatic peroxidation of lipids in the plasma membranes of thymocytes has been studied as affected by Ca2+. It is established that at calcium concentrations to 900 microM peroxidation gets more intensive; at higher concentrations of the intensity of this process falls.     

Inhibitory effect of female hormones on lipid peroxidation

The female hormones estradiol, estrone, and estriol acted as antioxidants in the peroxidation of methyl linoleate by UV irradiation. All of them inhibited the peroxidation of microsomal lipids when they were added to the ADP-Fe3+ peroxidation system of rat liver microsomes. The efficiencies in the microsomal system were in the order of estradiol greater than estriol greater than estrone.     

Antioxidant effect of caeruloplasmin on microsomal lipid peroxidation

Microsomal NADPH-dependent lipid peroxidation catalyzed by ADP-Fe³⁺ was inhibited by the addition of caeruloplasmin. The antioxidant effect of caeruloplasmin was independent of the superoxide anion (O^?₂ scavenging activity. Since caeruloplasmin enhanced the function of ADP-Fe³⁺ acting as electron acceptor for microsomal electron transport system, the antioxidant effect of caeruloplasmin is considered to depend on the ferroxidase activity.     

Inhibitory effect of phosphatidylserine on iron-dependent lipid peroxidation

The effect of phospholipids on lipid peroxidation was investigated in liposomal suspension of egg yolk phosphatidylcholine. Both saturated and unsaturated phosphatidylserine effectively inhibited lipid peroxidation induced by ferrous-ascorbate system in the presence of phosphatidylcholine hydroperoxides. Studies on the iron trapping effect of phospholipids indicated that the effectiveness of inhibition depends on the charge of phosphatidylserine that binds to free ionic iron.     

The effect of ionizing radiation on lipid peroxidation in rat blood

In experiments with 5-6 month male rats it was shown that whole-body gamma-irradiation (0.5 and 1.0 Gy) caused changes in the system of the antioxidant defence of the organism, the status of which influenced the intensity of lipid peroxidation in the blood.     

Steady magnetic fields effect on lipid peroxidation kinetics

The effect of steady magnetic fields (ranging from 0 to 280 mT) has been investigated on the kinetics of non-enzymatic lipid peroxidation occurring in a model system consisting of liposomes obtained from 1, 2-dioleoylphosphatidylcholine by oxygen consumption. The process was found to be accelerated by weak steady magnetic fields. A computer simulation method was employed to detect the reactions that govern the process kinetics, to elucidate magneto-sensitive stages (initiation and reduction of iron(III), as well as lipid peroxide radical recombination) and to determine their rate constants at various external magnetic fields. The kinetics of peroxidation of lipid cell membranes have been modeled mathematically at oxygen and ‘free’ iron concentrations close to those in the cells and also at increased free iron concentrations at different external magnetic field values.     

Role of lipid peroxidation in iron-induced cellular calcium overload

Calcium overload is the common pathway leading to cell injury. The role of iron-induced lipid peroxidation in the modification of Ehrlich carcinoma cells calcium homeostasis has been studied. There is a lack of correlation between that modification and the value of lipid peroxidation. The stability characteristics of low-mol-weight iron complexes affect lipid peroxidation and, to a lesser extent, cellular calcium uptake. Lipid peroxidation appears not as a triggering factor of cellular calcium homeostasis modification, but as a concomitant phenomenon.     

Induction of lipid peroxidation in calcium oxalate stone formation

The function of lipid peroxidation and the anti-peroxidative enzymes of rat liver and kidney were investigated under hyperoxaluric and stone forming conditions. The experimental animals showed higher malondialdehyde content in liver and kidney than that of control. A significant increase in malondialdehyde release was observed in the experimental liver or kidney when incubated with either ferrous sulphate or hydrogen peroxide compared to that of control liver or kidney. Superoxide dismutase activity was not affected in the hyperoxaluric rats while there was a moderate increase in the stone forming rats when compared to control. Highly significant decrease in catalase activity was observed in both conditions in liver and kidney compared to control.     

The effect of vitamin E on lipid peroxidation in the copper-deficient rat

The present study was designed to determine whether the supplementation of vitamin E in the copper-deficient diet would ameliorate the severity of copper deficiency in fructose-fed rats. Lipid peroxidation was measured in the livers and hearts of rats fed a copper-deficient diet (0.6 microg Cu/g) containing 62% fructose with adequate vitamin E (0.1 g/kg diet) or supplemented with vitamin E (1.0 g/kg diet). Hepatic lipid peroxidation was significantly reduced by vitamin E supplementation compared with the unsupplemented adequate rats. In contrast, myocardial lipid peroxidation was unaffected by the level of vitamin E. Regardless of vitamin E supplementation, all copper-deficient rats exhibited severe signs of copper deficiency, and some of the vitamin E-supplemented rats died of this deficiency. These findings suggest that although vitamin E provided protection against peroxidation in the liver, it did not protect the animals against the severity of copper deficiency induced by fructose consumption.     

The mechanism of NADPH-dependent lipid peroxidation. The propagation of lipid peroxidation.

NADPH-dependent lipid peroxidation occurs in two distinct sequential radical steps. The first step, initiation, is the ADP-perferryl ion-catalyzed formation of low levels of lipid hydroperoxides. The second step, propagation, is the iron-catalyzed breakdown of lipid hydroperoxides formed during initiation generating reactive intermediates and products characteristic of lipid peroxidation. Propagation results in the rapid formation of thiobarbituric acid-reactive material and lipid hydroperoxides. Propagation can be catalyzed by ethylenediamine tetraacetate-chelated ferrous ion, diethylenetriamine pentaacetic acid-chelated ferrous ion, or by ferric cytochrome P-450. However, cytochrome P-450 is destroyed during propagation.     

The effect of zinc on iron-induced lipid peroxidation in different lipid systems including liposomes and micelles

The effect of zinc on FeSO4/ascorbic acid-induced lipid peroxidation was measured by the thiobarbituric acid assay in various lipid systems including small unilamellar liposomes prepared from egg phosphatidylcholine (EPC), ionic micelles prepared from arachidonic acid (C20:4), non-ionic monocomponent micelles prepared from EPC-derived, methylated fatty acids, and an eicosatetrene emulsion. With the exception of C20:4 micelles, zinc inhibited lipid peroxidation in each of the above systems in a similar dose-related fashion, with 0.5 mM zinc having maximal effect. Gas-chromatographic fatty acid analysis too indicated a protective effect of zinc against FeCl3-induced lipid peroxidation in soybean PC vesicles, which do not contain C20:4 moieties. These findings, in particular the inhibition of lipid peroxidation in eicosatetrene emulsion, suggest that the presence of uncharged polar head groups, or packing of lipid molecules into ordered self-assemblages (membranes and micelles) have no critical influence on the antioxidant effect of zinc. The results with Fe2+ are compatible with the concept that zinc interferes with the formation of Fe2+-oxygen-enoic complexes. This mechanism, however, cannot account for the inhibition by zinc of the Fe#+-induced lipid peroxidation, suggesting the involvement of other types of zinc effects in these systems.     

Thiol antidotes effect on lipid peroxidation in mercury-poisoned rats

The effect of thiol antidotes 2,3-dimercapto-1-propanesulfonic acid (DMPS) and D-penicillamine (PA) on lipid peroxidation and on activities of some protecting enzymes in blood, liver and kidneys of mercury-poisoned rats has been studied. It has been found that Hg-poisoning is associated with increased lipid peroxidation in the liver and in the kidneys and with inactivation of superoxide dismutase (SOD) and catalase. Inhibition of SOD is caused by thiols treatment too, but in this case acceleration of lipid peroxidation has not been observed. Evidence is presented that in the liver, protection against mercury-induced lipid peroxidation is afforded by both thiols, while in the kidneys only PA has protective effect. In in vitro experiments it has been demonstrated that both antidotes can act as O2- scavengers and lipid peroxidation inhibitors, but PA is significantly more effective. On the basis of the obtained results a conclusion is drawn that in addition to the metal-removing ability, the antioxidant properties of the chelating agents may play an important role in manifestation of their beneficial effect in metal intoxications.     

The effect of histidine modification on copper-dependent lipid peroxidation in human low-density lipoprotein

Summary

Lipid peroxidation and subsequent oxidative modification of low-density lipoprotein (LDL) have been implicated as causal events in atherosclerosis. Cu²⁺ may play an important role in LDL oxidation by binding to histidine residues of apolipoprotein B-100 (apo B) and initiating and propagating lipid peroxidation. To investigate the role of histidine residues, we used diethylpyrocarbonate (DEPC), a lipid-soluble histidine-specific modifying reagent. When LDL (0.1 mg protein/ml, or 0.2 µM) was incubated with DEPC (1 mM), at least 76 ± 7% of the histidine residues in apo B were modified. Treatment of LDL with DEPC led to an increase in the rate of Cu²⁺-induced initiation of lipid peroxidation (R_i), but a significant decrease in the rate of propagation. These changes resulted in an overall increased resistance of LDL to oxidation, with a significantly increased lag phase preceding the propagation phase of lipid peroxidation. In contrast to DEPC, ascorbate completely prevented the initiation of LDL oxidation (R_i = 0). Our data indicate that there are two types of copper/histidine binding sites on apo B: those facing the lipid core of the LDL particle, which mediate the propagation of lipid peroxidation and are modified by DEPC; and those found on the surface of the LDL particle exposed to the aqueous environment, which are responsible for mediating the initiation of lipid peroxidation and are modifiable by ascorbate in the presence of Cu²⁺.