Nonenzymatic free radical-catalyzed generation of 15-deoxy-Δ12,14-prostaglandin J2-like compounds (deoxy-J2-isoprostanes) in vivo

Hardy, Klarissa D.; Cox, Brian E.; Milne, Ginger L.; Yin, Huiyong; Jackson, Klarissa D.

doi:10.1194/jlr.m010264

Cited by 29 publications

(24 citation statements)

References 59 publications

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“…These compounds readily dehydrate in vivo to yield A 2 /J 2 -IsoPs, which are also known as cyclopentenone IsoPs because they contain an α,β-unsaturated cyclopentenone ring structure [13,14]. A 2 /J 2 -IsoPs can be further metabolized, through rearrangement and dehydration, to yield deoxy-A 2 and deoxy-J 2 -IsoPs [15]. Hardy and colleagues have shown that 15-deoxy-Δ 12,14 -PGJ 2 (15-d-PGJ 2 ), a highly studied molecule originally identified as a metabolite of PGD 2 , can also be generated non-enzymatically during free radical-induced oxidation and is one of the deoxy-J 2 -IsoP isomers [15].…”

Section: Historical Perspectivementioning

confidence: 99%

“…A 2 /J 2 -IsoPs can be further metabolized, through rearrangement and dehydration, to yield deoxy-A 2 and deoxy-J 2 -IsoPs [15]. Hardy and colleagues have shown that 15-deoxy-Δ 12,14 -PGJ 2 (15-d-PGJ 2 ), a highly studied molecule originally identified as a metabolite of PGD 2 , can also be generated non-enzymatically during free radical-induced oxidation and is one of the deoxy-J 2 -IsoP isomers [15]. Finally, in addition to the molecules described above, compounds isomeric to the COX-derived thromboxane B 2 , termed isothromboxanes are products of the free radical-catalyzed peroxidation of arachidonic acid [16].…”

Section: Historical Perspectivementioning

confidence: 99%

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The isoprostanes—25 years later

Milne

Dai

Roberts

2015

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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275

237

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Isoprostanes (IsoPs) are prostaglandin-like molecules generated independent of the cyclooxygenase (COX) by the free radical-induced peroxidation of arachidonic acid. The first isoprostane species discovered were isomeric to prostaglandin F2α and were thus termed F2-IsoPs. Since the initial discovery of the F2-IsoPs, IsoPs with differing ring structures have been identified as well as IsoPs from different polyunsaturated fatty acids, including eicosapentaenoic acid and docosahexanenoic acid. The discovery of these molecules in vivo in humans has been a major contribution to the field of lipid oxidation and free radical research over the course of the past 25 years. These molecules have been determined to be both biomarkers and mediators of oxidative stress in numerous disease settings. This review focuses on recent developments in the field with an emphasis on clinical research. Special focus is given to the use of IsoPs as biomarkers in obesity, ischemia-reperfusion injury, the central nervous system, cancer, and genetic disorders. Additionally, attention is paid to diet and lifestyle factors that can affect endogenous levels of IsoPs. This article is part of a Special Issue entitled “Oxygenated metabolism of PUFA: analysis and biological relevance”.

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Section: Historical Perspectivementioning

confidence: 99%

Section: Historical Perspectivementioning

confidence: 99%

The isoprostanes—25 years later

Milne

Dai

Roberts

2015

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

Self Cite

275

237

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“…D2/E2-isoprostanes are formed in competition to F2-isoprostanes and the depletion of reducing agents such as α-tocopherol and ascorbic acid favours the formation of D2/E2-isoprostanes over that of F2-isoprostanes (Montine et al, 2003). D2/E2-isoprostanes can undergo further rearrangements generating A/J-isoprostanes, which are known as cyclopentenone isoprostanes (Chen et al, 1999a,b;Brooks et al, 2008;Hardy et al, 2011). Interestingly, degradation of A-isoprostane derivatives has been shown to occur during physiological conditions and has been demonstrated to give rise to biologically active intermediates (Benndorf et al, 2008).…”

Section: Formation Of Isoprostanesmentioning

confidence: 99%

Pathophysiology of isoprostanes in the cardiovascular system: implications of isoprostane‐mediated thromboxane A₂ receptor activation

Bauer

Ripperger

Frantz

et al. 2014

British J Pharmacology

133

109

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Isoprostanes are free radical-catalysed PG-like products of unsaturated fatty acids, such as arachidonic acid, which are widely recognized as reliable markers of systemic lipid peroxidation and oxidative stress in vivo. Moreover, activation of enzymes, such as COX-2, may contribute to isoprostane formation. Indeed, formation of isoprostanes is considerably increased in various diseases which have been linked to oxidative stress, such as cardiovascular disease (CVD), and may predict the atherosclerotic burden and the risk of cardiovascular complications in the latter patients. In addition, several isoprostanes may directly contribute to the functional consequences of oxidant stress via activation of the TxA2 prostanoid receptor (TP), for example, by affecting endothelial cell function and regeneration, vascular tone, haemostasis and ischaemia/reperfusion injury. In this context, experimental and clinical data suggest that selected isoprostanes may represent important alternative activators of the TP receptor when endogenous TxA2 levels are low, for example, in aspirin-treated individuals with CVD. In this review, we will summarize the current understanding of isoprostane formation, biochemistry and (patho) physiology in the cardiovascular context. IntroductionOxidative stress in biological systems is defined as an imbalance between the generation of reactive oxygen species (ROS) and antioxidant defence mechanisms (Dalle-Donne et al., 2006;Giustarini et al., 2009). In contrast to the physiological condition, during which ROS are only present at moderate levels and play an important role as messengers in redox signalling, in pathological conditions, when the physiological redox state of cells is disturbed, ROS can severely affect cellular signalling and function. Indeed, ROS which are not neutralized or scavenged by antioxidant molecules, such as GSH or superoxide dismutase, may react with nucleic acids and proteins and thereby alter the biochemical and physical properties of these important cellular components. Moreover, exposure of lipids to free radicals induces a non-enzymatic reaction cascade resulting in an increased formation of bioactive molecules named isoprostanes. Consequently, systemic isoprostane formation is significantly increased in a variety of pathological processes associated with oxidative stress, for example, cancer as well as, cardiovascular, metabolic and neurodegenerative diseases, and isoprostanes are increasingly recognized not only as markers of oxidative stress but also as mediators of disease progression (Praticò et al., 1997;Reilly et al., 1998;Davì et al., 1999;Minuz et al., 2002;Vassalle et al., 2003;Schwedhelm et al., 2004, Xia et al., 2005Montuschi et al., 2007;Schwedhelm et al., 2010; Barocas et al., 2011;Davies and Roberts, 2011; KhademAnsari et al., 2011;Montine et al., 2011;Sbardella et al., 2013). Isoprostanes are PG-like compounds derived from lipid peroxidation of esterified unsaturated fatty acids, for example, arachidonic acid, which are primarily generated in a free rad...

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“…COX can also form PGA 1 , the dehydrated product of PGE 1 , from dihomo-γ-linolenic acid (23). Nonenzymatic pathways of cyPG formation occur via the mechanisms described for isoP formation (24). …”

Section: Cyclopentenone Prostaglandinsmentioning

confidence: 99%

Redox-Dependent Anti-Inflammatory Signaling Actions of Unsaturated Fatty Acids

Delmastro-Greenwood

Freeman

Wendell

2014

Annu. Rev. Physiol.

102

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Unsaturated fatty acids are metabolized to reactive products that can act as pro- or anti-inflammatory signaling mediators. Electrophilic fatty acid species, including nitro- and oxo-containing fatty acids, display salutary anti-inflammatory and metabolic actions. Electrophilicity can be conferred by both enzymatic and oxidative reactions, via the homolytic addition of nitrogen dioxide to a double bond or via the formation of α,β-unsaturated carbonyl and epoxide substituents. The endogenous formation of electrophilic fatty acids is significant and influenced by diet, metabolic, and inflammatory reactions. Transcriptional regulatory proteins and enzymes can sense the redox status of the surrounding environment upon electrophilic fatty acid adduction of functionally significant, nucleophilic cysteines. Through this covalent and often reversible posttranslational modification, gene expression and metabolic responses are induced. At low concentrations, the pleiotropic signaling actions that are regulated by these protein targets suggest that some classes of electrophilic lipids may be useful for treating metabolic and inflammatory diseases.

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Nonenzymatic free radical-catalyzed generation of 15-deoxy-Δ12,14-prostaglandin J2-like compounds (deoxy-J2-isoprostanes) in vivo

Cited by 29 publications

References 59 publications

The isoprostanes—25 years later

The isoprostanes—25 years later

Pathophysiology of isoprostanes in the cardiovascular system: implications of isoprostane‐mediated thromboxane A₂ receptor activation

Redox-Dependent Anti-Inflammatory Signaling Actions of Unsaturated Fatty Acids

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Nonenzymatic free radical-catalyzed generation of 15-deoxy-Δ12,14-prostaglandin J2-like compounds (deoxy-J2-isoprostanes) in vivo

Cited by 29 publications

References 59 publications

The isoprostanes—25 years later

The isoprostanes—25 years later

Pathophysiology of isoprostanes in the cardiovascular system: implications of isoprostane‐mediated thromboxane A2 receptor activation

Redox-Dependent Anti-Inflammatory Signaling Actions of Unsaturated Fatty Acids

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Pathophysiology of isoprostanes in the cardiovascular system: implications of isoprostane‐mediated thromboxane A₂ receptor activation