The role of autophagy in survival response induced by 27-hydroxycholesterol in human promonocytic cells.

Autophagy has been shown to be stimulated in advanced atherosclerotic plaques by metabolic stress, inflammation and oxidized lipids. The lack of published studies addressing the potential stimulation of pro-survival autophagy by oxysterols, a family of cholesterol oxidation products, has prompted our study. Thus, the goal of the current study is to elucidate the molecular mechanism of the autophagy induced by 27-hydroxycholesterol (27-OH), that is one of the most abundant oxysterols in advanced atherosclerotic lesions, and to assess whether the pro-oxidant effect of the oxysterol is involved in the given response. Here we showed that 27-OH, in a low micromolar range, activates a pro-survival autophagic response in terms of increased LC3 II/LC3 I ratio and Beclin 1, that depends on the up-regulation of extracellular signal-regulated kinase (ERK) and phosphoinositide 3-kinase (PI3K)/Akt pathways as a potential result of an intracellular reactive oxygen species increase provoked by the oxysterol in human promonocytic U937 cells. Moreover, 27-OH induced autophagy is dependent on the relation between nuclear factor erythroid 2 p45-related factor 2 (Nrf2)-dependent antioxidant response and p62. The data obtained highlight the involvement of cholesterol oxidation products in the pathogenesis of oxidative stress related chronic diseases like atherosclerosis. Therefore, deeply understanding the complex mechanism and generating synthetic or natural molecules targeting this survival mechanism might be very promising tools in the prevention of such diseases. Keywords: Oxysterols, 27-hydroxycholesterol, Autophagy, ROS, Survival signalin

Bcl-2 protein family: Implications in vascular apoptosis and atherosclerosis

Apoptosis has been recognized as a central component in the pathogenesis of atherosclerosis, in addition to the other human pathologies such as cancer and diabetes. The pathophysiology of atherosclerosis is complex, involving both apoptosis and proliferation at different phases of its progression. Oxidative modification of lipids and inflammation differentially regulate the apoptotic and proliferative responses of vascular cells during progression of the atherosclerotic lesion. Bcl-2 proteins act as the major regulators of extrinsic and intrinsic apoptosis signalling pathways and more recently it has become evident that they mediate the apoptotic response of vascular cells in response to oxidation and inflammation either in a provocative or an inhibitory mode of action. Here we address Bcl-2 proteins as major therapeutic targets for the treatment of atherosclerosis and underscore the need for the novel preventive and therapeutic interventions against atherosclerosis, which should be designed in the light of molecular mechanisms regulating apoptosis of vascular cells in atherosclerotic lesions

The role of ascorbate in antioxidant protection of biomembranes: Interaction with vitamin E and coenzyme Q

One of the vital roles of ascorbic acid (vitamin C) is to act as an antioxidant to protect cellular components from free radical damage. Ascorbic acid has been shown to scavenge free radicals directly in the aqueous phases of cells and the circulatory system. Ascorbic acid has also been proven to protect membrane and other hydrophobic compartments from such damage by regenerating the antioxidant form of vitamin E. In addition, reduced coenzyme Q, also a resident of hydrophobic compartments, interacts with vitamin E to regenerate its antioxidant form. The mechanism of vitamin C antioxidant function, the myriad of pathologies resulting from its clinical deficiency, and the many health benefits it provides, are reviewed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44796/1/10863_2004_Article_BF00762775.pd

EFFECT OF THE LACTOPEROXIDASE SYSTEM ON THE ACTIVITY OF STARTER CULTURES FOR YOGURT PRODUCTION

The LP system in raw milk was activated by the addition of equimolar concentrations (0.25 mM) of hydrogen peroxide (H2O2) and thiocyanate (SCN) as KSCN and utilizing the inherent milk lactoperoxidase (LP). H2O2 and SCN- concentrations were determined during the experiments by using spectrophotometric methods and found to decrease to 1.5 mug/ml and 0.4 mug/ml respectively in 5 h. A relatively small amount of H2O2 was produced in the untreated milk which then was found to decrease. The activated sample, at the end of the 5 h period contained 10(9) cells/ml whereas the control sample contained 10(11) cells/ml. Lactic acid (LA) concentration inceased from 0.24 to 0.58% in the control after a slight delay of 1 h, whereas in the LP activated sample LA remained at a level 0.23 for 5 h. The activated LP system was found to delay the coagulation time and to strongly reduce the activity of starter cultures

Antioxidative and free radical scavenging properties of rosemary extract

Autoxidation of corn and soybean oils was prevented in the presence of 0.1 g/kg rosemary (Rosemarinus officinalis L.) extract and butylated hydroxy toluene (BHT). At the end of a 4-d period, the peroxide value in corn oil reached 13.0 and 8.2 in the presence of rosemary extract and BHT respectively. For soybean oil, the peroxide value was found to be 10.0 and 6.6 in the presence of rosemary extract and BHT respectively Rosemary extract and BHT when added as mixtures of 75:25, 50:50 and 25:75 had a synergistic effect on preventing oxidation of soybean oil. Superoxide radicals (O-2(.-)) were generated by phenazine methosulphate-NADH system and rosemary extract was found to scavenge O-2(.-) in a concentration-dependent manner. The antioxidative effect observed is believed to be partly due to this radical scavenger activity. (C) 1997 Academic Press Limited

Free radical scavenging and antioxidative properties of 'silibin' complexes on microsomal lipid peroxidation

The antioxidant properties of silibin complexes, the water-soluble form silibin dihemisuccinate (SDH), and the lipid-soluble form, silibin phosphatidylcholine complex known as IdB 1016, were evaluated by studying their abilities to react with the superoxide radical anion (O-2(-)), and the hydroxyl radical (OH.). In addition, their effect on pulmonary and hepatic microsomal lipid peroxidation had been investigated. Superoxide radicals were generated by the PMS-NADH system and measured by their ability to reduce NET. IC50 concentrations for the inhibition of the NET reduction by SDH and IdB 1016 were found to be 25 mu M and 316 mu M respectively. Both silibin complexes had an inhibitory effect on xanthine oxidase activity. SDH reacted rapidly with OH. radicals at approximately diffusion controlled rate and the rate constant was found to be (K = 8.2 x 10(9) M(-1) s(-1)); it appeared to chelate Fe2+ in solution