Thiyl radical attack on polyunsaturated fatty acids: A possible route to lipid peroxidation

Schöneich, Christian; Asmus, K.‐D.; Dillinger, Uwe; Bruchhausen, Franz von

doi:10.1016/0006-291x(89)91568-4

Cited by 105 publications

(38 citation statements)

References 11 publications

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“…Peroxynitrite-mediated oxidation of both low- [17] and high-molecular-weight thiols to thiyl radical intermediates (this report) may have several biological consequences since these radicals are reactive species which can initiate free radical chain reactions [29]. In the case of low-molecular-weight thiols such as glutathione it has been proposed that the thiyl radical can be detoxified, to some extent, by superoxide dismutase through the formation of oxidized glutathionyl radical anion which reacts with oxygen producing superoxide anion [30,31].…”

Section: Discussionmentioning

confidence: 94%

Peroxynitrite‐mediated oxidation of albumin to the protein‐thiyl free radical

1994

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Nitric oxide reacts with superoxide to produce peroxynitrite, which may be an important mediator of oxidant-induced cellular injury. Here we report that peroxynitrite is able to oxidize a protein, bovine serum albumin (BSA), to the corresponding protein-thiyl free radical as demonstrated by electron pararnagnetic resonance (EPR)-spin-trapping experiments with both et-phenyl-N-tert-butyl nitrone (PBN) and 5,5-dimethyl-l-pyrroline-N-oxide (DMPO). BSA radical adduct yields increased with pH indicating peroxynitrite anion as its main forming agent. Reaction with peroxynitrite may be another aspect of the antioxidant action of albumin in extracellular fluids.

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Section: Discussionmentioning

confidence: 94%

Peroxynitrite‐mediated oxidation of albumin to the protein‐thiyl free radical

1994

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“…Although cytotoxicity was not specific to homocysteine, endothelial cell detachment is also observed with cysteine (Dudman et al, 1991), an increase in the hydrogen peroxidesensitive cellular fluorescent probe, 2',7'-dichlorofluorescein, was observed in cultured endothelial cells exposed to homocysteine (Toborek and Hennig, 1996). Besides the initiation of lipid peroxidation at the cell surface, homocysteine auto-oxidation with trace metal ions, generating reactive oxygen species such as superoxide anion, hydrogen peroxide, hydroxyl, and thiol free radicals (Munday, 1989;Schöneich et al, 1989), would directly oxidize low-density lipoprotein (LDL) (Heinecke et al, 1987;Hirano et al, 1994;Wood and Graham, 1995). Homocysteine would also contribute to the LDL oxidative modifications mediated by endothelial cells, macrophages, and smooth muscle cells (Heinecke et al, 1987;Sparrow and Olszewski, 1993;Wood and Graham, 1995), which are deeply involved in the initial steps of atherogenesis.…”

Section: Hyperhomocysteinemia-mediated Oxidant Stress Through Imbalanmentioning

confidence: 99%

Impaired Homocysteine Metabolism and Atherothrombotic Disease

Durand

Prost²,

Loreau

et al. 2001

Laboratory Investigation

228

147

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SUMMARY:Based on recent retrospective, prospective, and experimental studies, mild to moderate elevation of fasting or postmethionine-load plasma homocysteine is accepted as an independent risk factor for cardiovascular disease and thrombosis in both men and women. Hyperhomocysteinemia results from an inhibition of the remethylation pathway or from an inhibition or a saturation of the transsulfuration pathway of homocysteine metabolism. The involvement of a high dietary intake of methionine-rich animal proteins has not yet been investigated and cannot be ruled out. However, folate deficiency, either associated or not associated with the thermolabile mutation of the N 5,10 -methylenetetrahydrofolate reductase, and vitamin B 6 deficiency, perhaps associated with cystathionine ␤-synthase defects or with methionine excess, are believed to be major determinants of the increased risk of cardiovascular disease related to hyperhomocysteinemia. Recent experimental studies have suggested that moderately elevated homocysteine levels are a causal risk factor for atherothrombotic disease because they affect both the vascular wall structure and the blood coagulation system. The oxidant stress that results from impaired homocysteine metabolism, which modifies the intracellular redox status, might play a central role in the molecular mechanisms underlying moderate hyperhomocysteinemia-mediated vascular disorders. Because folate supplementation can efficiently reduce plasma homocysteine levels, both in the fasting state and after methionine loading, results from further prospective cohort studies and from on-going interventional trials will determine whether homocysteine-lowering therapies can contribute to the prevention and reduction of cardiovascular risk. Additionally, these studies will provide unequivocal arguments for the independent and causal relationship between hyperhomocysteinemia and atherothrombotic disease. (Lab Invest 2001, 81:645-672).C ardiovascular diseases remain the leading cause of mortality in Western populations. Hyperlipoproteinemia, hypertension, diabetes, obesity, and tobacco smoking are the main risk factors for atherosclerosis and its thrombotic complications. However, these factors alone cannot account for all of the deaths caused by vascular pathologies.As early as 1969, clinical studies conducted in homocystinuric children revealed the importance of severe hyperhomocysteinemia in premature development of atherosclerosis and thromboembolism (McCully, 1983). According to numerous retrospective case-controlled studies, moderate increases in plasma homocysteine, which can be precisely quantitated by high performance liquid chromatography (HPLC), raise the risk for cardiovascular disease 2-fold, after adjusting for classic risk factors. Moreover, up to 20% to 40% of patients with vascular pathologies present moderate to intermediate hyperhomocysteinemia. However, results from prospective studies are inconsistent. Additionally, molecular mechanisms underlying hyperhomocysteinemia-induced vascular diseas...

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“…Hydrogen abstraction by nitrogen dioxide, thiyl, and thiyl- sulfonyl radicals from PUFAs generate pentadienyl radicals (41,42,68), which act as radical precursors in the chain of lipid peroxidation (43). Although deviations from homogeneous reaction kinetics are expected within cells, rate constants for radical-scavenging by ␤-carotene compare favorably with the corresponding rates of hydrogen abstraction from PUFAs.…”

mentioning

confidence: 92%

“…Thiyl radicals are synonymous with the classical repair reactions of thiols in vivo (36,37) and are also generated by peroxidasecatalyzed oxidation of thiols (38,39). Although the fate of RS ⅐ radicals within cells remains a matter for debate (40), there is increasing evidence to suggest that they are capable of initiating the chain of lipid peroxidation at least in model systems (41)(42)(43). Thiyl radicals undergo conjugation with molecular oxygen to generate the thiyl peroxyl (RSOO ⅐ ) radical (44) which can rearrange to thiyl-sulfonyl (RSO 2 ⅐ ) radical (45), another potent initiator of lipid peroxidation (46).…”

mentioning

confidence: 99%

Scavenging of Nitrogen Dioxide, Thiyl, and Sulfonyl Free Radicals by the Nutritional Antioxidant ²-Carotene

Everett

Dennis

Patel

et al. 1996

Journal of Biological Chemistry

186

143

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؉ and radical-addition, [RSO 2 ⅐⅐⅐␤-carotene] ⅐ in an approximate 3:1 ratio. The ␤-carotene radical-cation and adduct-radicals are highly resonance stabilized and undergo slow bimolecular decay to non-radical products. These carotenoidderived radicals react differently with oxygen, a factor which is expected to influence the antioxidant activity of ␤-carotene within tissues of varying oxygen tension in vivo.

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Thiyl radical attack on polyunsaturated fatty acids: A possible route to lipid peroxidation

Cited by 105 publications

References 11 publications

Peroxynitrite‐mediated oxidation of albumin to the protein‐thiyl free radical

Peroxynitrite‐mediated oxidation of albumin to the protein‐thiyl free radical

Impaired Homocysteine Metabolism and Atherothrombotic Disease

Scavenging of Nitrogen Dioxide, Thiyl, and Sulfonyl Free Radicals by the Nutritional Antioxidant ²-Carotene

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