A series of prostaglandin F2-like compounds are produced in vivo in humans by a non-cyclooxygenase, free radical-catalyzed mechanism.

Morrow, Jason D.; Hill, Kristina E.; Burk, Raymond F.; Nammour, Tarek; Badr, Kamal F.; Roberts, L. Jackson

doi:10.1073/pnas.87.23.9383

Cited by 1,754 publications

(1,238 citation statements)

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“…Regarding the potential significance of 8-iso-PGF 2α signaling, it is important to note that isoprostanes can be produced in vivo at levels that are several orders of magnitude higher than classical prostaglandins/thromboxanes [2]. Consequently, the biological effects of these signaling pathways could substantially impact cellular function in vivo.…”

Section: Discussionmentioning

confidence: 99%

“…While the prostaglandins are produced as a result of cyclooxygenase enzyme activity, isoprostanes are generally thought to form nonenzymatically by free radical-mediated peroxidation of arachidonic acid (AA) [2]. Separate evidence has suggested that cyclooxygenase activity may also contribute to isoprostane production in selected tissues [3,4].…”

Section: Introductionmentioning

confidence: 99%

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Characterization of isoprostane signaling: Evidence for a unique coordination profile of 8-iso-PGF2α with the thromboxane A2 receptor, and activation of a separate cAMP-dependent inhibitory pathway in human platelets

Khasawneh

Huang

Mir

et al. 2008

Biochemical Pharmacology

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Since isoprostanes are thought to participate in the pathogenesis of thrombosis, presumably through their interaction with thromboxane receptors (TPRs), we examined the ability of 8-iso-PGF 2α to bind/signal through TPRs. Using TPR expressing HEK cells, it was found that 8-iso-PGF 2α mobilized calcium and bound TPRs with a dissociation constant (K d ) of 57 nM. Interestingly, site-directed-mutagenesis revealed that 8-iso-PGF 2α has a unique coordination profile with TPRs. Thus, while Phe 184 and Asp 193 are shared by both 8-iso-PGF 2α and classical TPR ligands, Phe 196 was found to be required only for 8-iso-PGF 2α binding. Functional studies also revealed interesting results. Namely, that 8-iso-PGF 2α signals in human platelets through both a stimulatory (TPR-dependent) and an inhibitory (cAMP-dependent) pathway. Consistent with the existence of two signaling pathways, platelets were also found to possess two separate binding sites for 8-iso-PGF 2α . While the stimulatory site is represented by TPRs, the second cAMP inhibitory site is presently unidentified, but does not involve receptors for PGI 2 , PGD 2 or PGE 2 . In summary, these studies provide the first documentation that: (1) 8-iso-PGF 2α coordinates with Phe 184 , Asp 193 and Phe 196 on platelet TPRs; (2) Phe 196 serves as a unique TPR binding site for 8-iso-PGF 2α ; (3) 8-iso-PGF 2α signals through both stimulatory and inhibitory pathways in platelets; (4) 8-iso-PGF 2α inhibits human platelet activation through a cAMP-dependent mechanism; (5) 8-iso-PGF 2α interacts with platelets at two separate binding sites. Collectively, these results provide evidence for a novel isoprostane function in platelets which is mediated through a cAMP-coupled receptor.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Characterization of isoprostane signaling: Evidence for a unique coordination profile of 8-iso-PGF2α with the thromboxane A2 receptor, and activation of a separate cAMP-dependent inhibitory pathway in human platelets

Khasawneh

Huang

Mir

et al. 2008

Biochemical Pharmacology

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“…The isoprostanes were originally discovered in 1990 by Morrow et al, [64] and are now believed to act as potent mediators of oxidative injury [64][65][66][67][68]. As such, the isoprostanes are mainly generated from arachidonic acid non-enzymatically and are synthesised in situ in phospholipids and then released through the actions of phospholipases, such as phospholipase A 2 [64,65]. A wide range of prostanoid-like isoprostanes is generated including the PGF 2α -, the PGD 2 -, and PGE 2 -series [64,69].…”

Section: Isoprostanes and Tp Receptor Activationmentioning

confidence: 99%

“…As such, the isoprostanes are mainly generated from arachidonic acid non-enzymatically and are synthesised in situ in phospholipids and then released through the actions of phospholipases, such as phospholipase A 2 [64,65]. A wide range of prostanoid-like isoprostanes is generated including the PGF 2α -, the PGD 2 -, and PGE 2 -series [64,69]. The F 2 series are the most common and one of these compounds 8-epi PGF 2α , also recently termed iPF 2α -III [69], is the most abundant isoprostane generated in situations of oxidative injury [64][65][66][67][68][69].…”

Section: Isoprostanes and Tp Receptor Activationmentioning

confidence: 99%

Thromboxane A2 Signalling in Humans: a ‘Tail’ of Two Receptors

Kinsella

2001

Biochem. Soc. Trans

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“…8‐Epi‐prostaglandin F 2α (8‐epi‐PGF 2α ) is formed from peroxidation of arachidonic acid19 and is detectable in human plasma and urine. The quantification of 8‐epi‐PGF 2α has been widely used as a noninvasive method to assess lipid peroxidation 20, 21.…”

Section: Introductionmentioning

confidence: 99%

Short‐Term Exposure to Air Pollution and Biomarkers of Oxidative Stress: The Framingham Heart Study

Wilker

Dorans

et al. 2016

JAHA

122

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BackgroundShort‐term exposure to elevated air pollution has been associated with higher risk of acute cardiovascular diseases, with systemic oxidative stress induced by air pollution hypothesized as an important underlying mechanism. However, few community‐based studies have assessed this association.Methods and ResultsTwo thousand thirty‐five Framingham Offspring Cohort participants living within 50 km of the Harvard Boston Supersite who were not current smokers were included. We assessed circulating biomarkers of oxidative stress including blood myeloperoxidase at the seventh examination (1998–2001) and urinary creatinine‐indexed 8‐epi‐prostaglandin F2α (8‐epi‐PGF 2α) at the seventh and eighth (2005–2008) examinations. We measured fine particulate matter (PM 2.5), black carbon, sulfate, nitrogen oxides, and ozone at the Supersite and calculated 1‐, 2‐, 3‐, 5‐, and 7‐day moving averages of each pollutant. Measured myeloperoxidase and 8‐epi‐PGF 2α were loge transformed. We used linear regression models and linear mixed‐effects models with random intercepts for myeloperoxidase and indexed 8‐epi‐PGF 2α, respectively. Models were adjusted for demographic variables, individual‐ and area‐level measures of socioeconomic position, clinical and lifestyle factors, weather, and temporal trend. We found positive associations of PM 2.5 and black carbon with myeloperoxidase across multiple moving averages. Additionally, 2‐ to 7‐day moving averages of PM 2.5 and sulfate were consistently positively associated with 8‐epi‐PGF 2α. Stronger positive associations of black carbon and sulfate with myeloperoxidase were observed among participants with diabetes than in those without.ConclusionsOur community‐based investigation supports an association of select markers of ambient air pollution with circulating biomarkers of oxidative stress.

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A series of prostaglandin F2-like compounds are produced in vivo in humans by a non-cyclooxygenase, free radical-catalyzed mechanism.

Cited by 1,754 publications

References 14 publications

Characterization of isoprostane signaling: Evidence for a unique coordination profile of 8-iso-PGF2α with the thromboxane A2 receptor, and activation of a separate cAMP-dependent inhibitory pathway in human platelets

Characterization of isoprostane signaling: Evidence for a unique coordination profile of 8-iso-PGF2α with the thromboxane A2 receptor, and activation of a separate cAMP-dependent inhibitory pathway in human platelets

Thromboxane A2 Signalling in Humans: a ‘Tail’ of Two Receptors

Short‐Term Exposure to Air Pollution and Biomarkers of Oxidative Stress: The Framingham Heart Study

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