Hypochlorite induces lipid peroxidation in blood lipoproteins and phospholipid liposomes

Панасенко, О. М.; Evgina, S. A.; Driomina, Elena S.; Sharov, Victor S.; Сергиенко, В. И.; Vladimirov, Yu. A.

doi:10.1016/0891-5849(94)00211-2

Cited by 58 publications

(28 citation statements)

References 19 publications

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“…BHT reportedly even completely inhibits TBArS formation in VLDL and phosphatidylcholine vesicles treated with hypochlorite for up to 3 hours. 42 On the other hand, some oxidative modification of the lipid moiety of LDL still may occur. Treatment of phospholipids with hypochlorite could lead to the formation of products not detectable by the methods applied in the present study, eg, the accumulation of small amounts of lysolecithin, chloramines, and other oxidative products derived from the polar part of phospholipids.…”

Section: Discussionmentioning

confidence: 99%

Modification of Protein Moiety of Human Low Density Lipoprotein by Hypochlorite Generates Strong Platelet Agonist

Volf

Bielek

Moeslinger

et al. 2000

ATVB

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Abstract-Conflicting reports exist about the effects of mildly or extensively oxidized low density lipoproteins (LDLs) on the reactivity of human platelets. This platelet response is mainly caused by modification of the protein and lipid moiety, giving rise to very differently modified species with hardly predictable properties. The aim of this study was to prepare oxidized LDL with modifications essentially restricted to the protein moiety and to determine the eventual platelet responses. We treated LDL at 0°C for 10 minutes with a 60-to 1000-fold molar excess of sodium hypochlorite in borate buffer in the presence of the radical scavenger butylated hydroxytoluene. Under these conditions, neither fragmentation of apolipoprotein B-100 nor formation of LDL aggregates was observed, and lipid oxidation products did not exceed the amount present in untreated LDLs. The degree of modification and the respective effects on platelet function were highly reproducible. Hypochlorite-modified LDLs act as strong platelet agonists, inducing morphological changes, dense granule release, and irreversible platelet aggregation. The evoked platelet effects are completely suppressed by inhibitors of the phosphoinositide cycle but not by EDTA or acetylsalicylic acid. Most likely, these effects are transmitted via high-affinity binding to a single class of sites, which does not recognize native or acetylated LDL. Obviously, modified lysines, and the secondary lipid modifications derived from them, are not essential for this interaction. We conclude that bioactive oxidized lipids are not directly involved in the stimulation of platelets by hypochlorite-modified LDLs. Key Words: atherosclerosis Ⅲ oxidized LDL Ⅲ apoB-100 Ⅲ human platelets Ⅲ platelet aggregation P latelet-vessel wall interaction (adhesion) and plateletplatelet interaction (aggregation) play a central role in vascular occlusion but are also involved in the earlier stages of development of atherosclerotic plaques. 1 Therefore, conditions leading to altered platelet function are accompanied with an enhanced risk of atherosclerosis and thrombosis. 2 Among others, severe disorders of plasma lipids lead to enhanced platelet reactivity. In particular, it has been known for Ͼ25 years that platelets from hyperlipidemic patients are hyperreactive. 3 Furthermore, LDLs from patients with homozygous familial hypercholesterolemia show enhanced susceptibility to oxidative modification, 4 thus generating a form that is substantially more atherogenic than unmodified LDLs. 5 Native LDLs (nLDLs) reportedly stimulate human platelets, 6,7 but minimally modified LDLs rather than nLDLs may be responsible for these effects. 8,9 LDLs oxidized in vitro by various agents (oxLDLs) showed even more pronounced platelet activation. 10 Because activated platelets may themselves contribute to oxidative modification of LDLs, 11 the platelet-stimulatory effect of plasma lipoproteins is potentially a key event in atherogenesis.Free radicals as well as nonradical oxidants are involved in the oxidative modif...

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Section: Discussionmentioning

confidence: 99%

Modification of Protein Moiety of Human Low Density Lipoprotein by Hypochlorite Generates Strong Platelet Agonist

Volf

Bielek

Moeslinger

et al. 2000

ATVB

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“…Myeloperoxidase expressed in neutrophils and macrophages catalyzes a reaction between hydrogen peroxide and chloride that yields hypochlorite, a strong oxidizing agent (Panasenko et al, 1995;Weiss, 1989). These ROS in the spinal lesion react with polyunsaturated fatty acids and result in lipid peroxidation and membrane damage.…”

Section: The Anti-cd11d Treatment Reduces Markers Of Secondary Damagementioning

confidence: 99%

CD11d Antibody Treatment Improves Recovery in Spinal Cord-Injured Mice

Geremia

Feng²,

Rosenzweig³

et al. 2012

Journal of Neurotrauma

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Acute administration of a monoclonal antibody (mAb) raised against the CD11d subunit of the leukocyte CD11d/CD18 integrin after spinal cord injury (SCI) in the rat greatly improves neurological outcomes. This has been chiefly attributed to the reduced infiltration of neutrophils into the injured spinal cord in treated rats. More recently, treating spinal cord-injured mice with a Ly-6G neutrophil-depleting antibody was demonstrated to impair neurological recovery. These disparate results could be due to different mechanisms of action utilized by the two antibodies, or due to differences in the inflammatory responses between mouse and rat that are triggered by SCI. To address whether the anti-CD11d treatment would be effective in mice, a CD11d mAb (205C) or a control mAb (1B7) was administered intravenously at 2, 24, and 48 h after an 8-g clip compression injury at the fourth thoracic spinal segment. The anti-CD11d treatment reduced neutrophil infiltration into the injured mouse spinal cord and was associated with increased white matter sparing and reductions in myeloperoxidase (MPO) activity, reactive oxygen species, lipid peroxidation, and scar formation. These improvements in the injured spinal cord microenvironment were accompanied by increased serotonin (5-HT) immunoreactivity below the level of the lesion and improved locomotor recovery. Our results with the 205C CD11d mAb treatment complement previous work using this anti-integrin treatment in a rat model of SCI.

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“…Lipid peroxidation in isolated LDL exposed to hypochlorite is reported by several groups to occur following apoB modifi cation by breakdown of chloramines which, in turn, produces radicals [96] . The method used by Coleman et al to modify LDL by hypochlorite might result in similar reactions as described [92,94] , because the modifi cation procedure was performed without cooling, and excessive hypochlorite was not removed, thereby driving the reaction further. The results disagree in several points with the results of the aforementioned papers.…”

Section: Hypochlorite Modifi Cation Of Ldlmentioning

confidence: 99%

“…Furthermore, 10 m M 3-chloro-tyrosine proved ineffective in activating platelets (E Koller, unpublished). With no plausible amino acid modifi cation held responsible for the reported effects on platelet aggregation, one might speculate that they actually go back to lipid-oxidation products formed subsequent to the hypochlorite reaction with the protein moiety, involving free radicals or free reactive oxygen species [92,94,96] . For hypoxLDL-induced platelet activation, these reactants should not be important, since scavengers like catalase had no effect on the platelet-hypoxLDL interactions [108] .…”

Section: Hypochlorite Modifi Cation Of Ldlmentioning

confidence: 99%

“…In marked contrast to most other oxidative pathways, this oxidant transforms LDL into a high uptake form (hypoxLDL) without signifi cant formation of LPO [89,90] . The onset of modifi cation of the lipid moiety, and the rate and degree of formation of lipid hydroperoxides and of secondary products of lipid oxidation largely depend on the reaction conditions [91][92][93][94] . Unlike oxidation methods based on reactive oxygen or nitrogen species, however, HOCl-driven in vitro oxidation can be controlled in a fairly reproducible manner, as long as it is mainly confi ned to the protein moiety.…”

Section: +mentioning

confidence: 99%

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Modified Low-Density Lipoproteins and High-Density Lipoproteins

Koller

Volf

Gurvitz

et al. 2006

Pathophysiol Haemos Thromb

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It has long been known that the oxidative state of the various plasma lipoproteins modulates platelet aggregability, thereby contributing to atherogenesis. Low-density lipoprotein (LDL), occurring in vivo both in the native and oxidised forms, interacts directly with platelets, by binding to specific receptors. While the identity of the receptors for native LDL and some subfractions of high-density lipoproteins (HDL) remains disputed, apoE-containing HDL₂ binds to LRP8. The nature of these interactions as well as the distinction between candidate receptor proteins was elucidated using covalently modified apolipoproteins, which pointed to the participation of apolipoproteins in high affinity binding. However, the platelet effects initiated by binding of native lipoproteins remain controversial. Some of this ambiguity can be traced to the fact that native LDL inevitably undergoes substantial oxidisation upon modification, including by radiolabelling. The platelet-activating effects provoked by oxidised LDL are irrefutable, but many details remain unknown. The role of CD36 in platelet binding by oxidised LDL is well established, although additional receptors may exist. Much less is known about the interaction of oxidised HDL with platelets, since platelet activation was observed in some, but not all studies. Various frequently applied in vitro oxidation methods produce modified lipoprotein species that may not be relevant in vivo. Based on the reported modifications obtained by in vitro oxidation of LDL, early investigations focused mainly on the formation and the eventual effects of oxidised lipids. More recently, alterations to lipoproteins performed using hypochloric acid and myeloperoxidase redirected the attention to the role of modified apoproteins in triggering platelet responses.

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Hypochlorite induces lipid peroxidation in blood lipoproteins and phospholipid liposomes

Cited by 58 publications

References 19 publications

Modification of Protein Moiety of Human Low Density Lipoprotein by Hypochlorite Generates Strong Platelet Agonist

Modification of Protein Moiety of Human Low Density Lipoprotein by Hypochlorite Generates Strong Platelet Agonist

CD11d Antibody Treatment Improves Recovery in Spinal Cord-Injured Mice

Modified Low-Density Lipoproteins and High-Density Lipoproteins

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