Free Radical Lipid Peroxidation: Mechanisms and Analysis

Yin, Huiyong; Xu, Libin; Porter, Ned A.

doi:10.1021/cr200084z

Cited by 1,464 publications

(1,355 citation statements)

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“…The sequence of reactions in lipid peroxidation has been described previously in many informative reviews [11][12][13][14][15][16][17][18], and will only be outlined briefly here. The essence is that free radical oxidants can abstract a hydrogen atom from bis-allylic carbons in the PUFA chains to form a carbon-centred radical (L • ).…”

Section: Lipid Peroxidation and Its Primary Productsmentioning

confidence: 99%

“…This unstable primary intermediate reacts readily with molecular oxygen (which has a di-radical ground state), resulting in formation of a lipid peroxyl radical (LOO • ). This is also a reactive radical and in a lipid bilayer is able to abstract a hydrogen atom from an adjacent fatty acyl chain, thus forming a hydroperoxide (LOOH) and propagating the radical chain reaction [16]. Alternatively, the peroxyl radical can attack intramolecularly to yield a dioxetane or an endoperoxide.…”

Section: Lipid Peroxidation and Its Primary Productsmentioning

confidence: 99%

“…Lipid hydroperoxides or peroxyl radicals can undergo fragmentation by enzymatic or non-enzymatic mechanisms to produce short-chain oxidation products, including a variety of different aldehydes, alkanes and alkenes [13,16], of which malondialdehyde (MDA) and 4-hydroxy-2-nonenal (HNE) are by far the most studied [17]. Table 1 illustrates the wide variety of products that have been detected following oxidative fragmentation of PUFAs.…”

Section: Aldehydes Are Fragmentation Products Of Oxidized Lipidsmentioning

confidence: 99%

“…There are three main mechanisms by which a carbon-carbon bond can be cleaved, as described and reviewed in several key publications by researchers at Vanderbilt University and elsewhere [16,[24][25][26][27]. The principles have mostly commonly been explored with linoleic acid and have focused on the formation of 4-hydroxy-2-nonenal (HNE), owing to the fact that it is one of the most abundantly formed lipid peroxidation products and has interesting biological effects [8,28,29].…”

Section: Aldehydes Are Fragmentation Products Of Oxidized Lipidsmentioning

confidence: 99%

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Chemistry and analysis of HNE and other prominent carbonyl-containing lipid oxidation compounds

Sousa

Pitt

Spickett

2017

Free Radical Biology and Medicine

143

105

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The process of lipid oxidation generates a diverse array of small aldehydes and carbonyl-containing compounds, which may occur in free form or esterified within phospholipids and cholesterol esters. These aldehydes mostly result from fragmentation of fatty acyl chains following radical oxidation, and the products can be subdivided into alkanals, alkenals (usually D,β-unsaturated), γ-substituted alkenals and bis-aldehydes.Isolevuglandins are non-fragmented di-carbonyl compounds derived from H 2 -isoprostanes, and oxidation of the ω-3-fatty acid docosahexenoic acid yield analogous 22 carbon neuroketals. Non-radical oxidation by hypochlorous acid can generate D-chlorofatty aldehydes from plasmenyl phospholipids. Most of these compounds are reactive and have generally been considered as toxic products of a deleterious process. The reactivity is especially high for the D,β-unsaturated alkenals, such as acrolein and crotonaldehyde, and for γ-substituted alkenals, of which 4-hydroxy-2-nonenal and 4-oxo-2-nonenal are best Page | 2 known. Nevertheless, in recent years several previously neglected aldehydes have been investigated and also found to have significant reactivity and biological effects; notable examples are 4-hydroxy-2-hexenal and 4-hydroxy-dodecadienal. This has led to substantial interest in the biological effects of all of these lipid oxidation products and their roles in disease, including proposals that HNE is a second messenger or signalling molecule.However, it is becoming clear that many of the effects elicited by these compounds relate to their propensity for forming adducts with nucleophilic groups on proteins, DNA and specific phospholipids. This emphasizes the need for good analytical methods, not just for free lipid oxidation products but also for the resulting adducts with biomolecules. The most informative methods are those utilizing HPLC separations and mass spectrometry, although analysis of the wide variety of possible adducts is very challenging. Nevertheless, evidence for the occurrence of lipid-derived aldehyde adducts in biological and clinical samples is building, and offers an exciting area of future research. AbbreviationsAcr-dG, 1,N2-propanodeoxyguanosine; AGEs, advanced glycation end-product; ALEs, advanced lipoxidation end product; ApoB100, apolipoprotein B100; ApoE, apolipoprotein E; ARP, aldehyde reactive probe; AspN, endoproteinase AspN (flavastacin); βLG, β-lactoglobulin; BHZ, biotin hydrazide; BN-PAGE, blue native polyacrylamide gel

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Section: Lipid Peroxidation and Its Primary Productsmentioning

confidence: 99%

Section: Lipid Peroxidation and Its Primary Productsmentioning

confidence: 99%

Section: Aldehydes Are Fragmentation Products Of Oxidized Lipidsmentioning

confidence: 99%

Section: Aldehydes Are Fragmentation Products Of Oxidized Lipidsmentioning

confidence: 99%

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Chemistry and analysis of HNE and other prominent carbonyl-containing lipid oxidation compounds

Sousa

Pitt

Spickett

2017

Free Radical Biology and Medicine

143

105

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“…18 Analogous chemistry occurring within the epithelial lining would release hydroperoxyl radicals initiating lipid peroxidation 19 and cysteine sulfinyl radicals that have been implicated in enzyme inactivation pathways. 20 …”

Section: Introductionmentioning

confidence: 99%

Radical Formation in the Gas‐Phase Ozonolysis of Deprotonated Cysteine

et al. 2015

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Although the deleterious effects of ozone on the human respiratory system are well-known, many of the precise chemical mechanisms that both cause damage and afford protection in the pulmonary epithelial lining fluid are poorly understood. As a key first step to elucidating the intrinsic reactivity of ozone with proteins, its reactions with deprotonated cysteine [Cys−H]− are examined in the gas phase. Reaction proceeds at near the collision limit to give a rich set of products including 1) sequential oxygen atom abstraction reactions to yield cysteine sulfenate, sulfinate and sulfonate anions, and significantly 2) sulfenate radical anions formed by ejection of a hydroperoxy radical. The free-radical pathway occurs only when both thiol and carboxylate moieties are available, implicating electron-transfer as a key step in this reaction. This novel and facile reaction is also observed in small cys-containing peptides indicating a possible role for this chemistry in protein ozonolysis. [b] Timothy M. Benton, [a] Tony Ly, [b] Gabriel da Silva, [c] Stephen J. Blanksby, [d] * and Richard A. J. O'Hair, [a] * Abstract: Although the deleterious effects of ozone on the human respiratory system are well known, many of the precise chemical mechanisms that both cause damage and afford protection in the pulmonary epithelial lining fluid are poorly understood. As a key first step to elucidating the intrinsic reactivity of ozone with proteins, its reactions with deprotonated cysteine [Cys-H] -are examined in the gas phase. Reaction proceeds at near the collision limit to give a rich set of products including (i) sequential O atom abstraction reactions to yield cysteine sulfenate, sulfinate and sulfonate anions, and significantly (ii) sulfenate radical anions formed by ejection of a hydroperoxyl radical. The free radical pathway occurs only where both thiol and carboxylate moieties are available implicating electron-transfer as a key step in this reaction. This novel and facile reaction is also observed in small cys-containing peptides indicating a possible role for this chemistry in protein ozonolysis.

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The role of ferroptosis as a regulator of oxidative stress in the pathogenesis of ischemic stroke

Delgado‐Martín,

Martínez‐Ruiz

2024

FEBS Letters

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Ferroptosis is a unique form of cell death that was first described in 2012 and plays a significant role in various diseases, including neurodegenerative conditions. It depends on a dysregulation of cellular iron metabolism, which increases free, redox‐active, iron that can trigger Fenton reactions, generating hydroxyl radicals that damage cells through oxidative stress and lipid peroxidation. Lipid peroxides, resulting mainly from unsaturated fatty acids, damage cells by disrupting membrane integrity and propagating cell death signals. Moreover, lipid peroxide degradation products can further affect cellular components such as DNA, proteins, and amines. In ischemic stroke, where blood flow to the brain is restricted, there is increased iron absorption, oxidative stress, and compromised blood–brain barrier integrity. Imbalances in iron‐transport and ‐storage proteins increase lipid oxidation and contribute to neuronal damage, thus pointing to the possibility of brain cells, especially neurons, dying from ferroptosis. Here, we review the evidence showing a role of ferroptosis in ischemic stroke, both in recent studies directly assessing this type of cell death, as well as in previous studies showing evidence that can now be revisited with our new knowledge on ferroptosis mechanisms. We also review the efforts made to target ferroptosis in ischemic stroke as a possible treatment to mitigate cellular damage and death.

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Free Radical Lipid Peroxidation: Mechanisms and Analysis

Cited by 1,464 publications

References 233 publications

Chemistry and analysis of HNE and other prominent carbonyl-containing lipid oxidation compounds

Chemistry and analysis of HNE and other prominent carbonyl-containing lipid oxidation compounds

Radical Formation in the Gas‐Phase Ozonolysis of Deprotonated Cysteine

The role of ferroptosis as a regulator of oxidative stress in the pathogenesis of ischemic stroke

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