Oxidized phosphatidylcholines are produced in renal ischemia reperfusion injury

Solati, Zahra; Edel, Andrea L.; Shang, Yue; Karmin, O; Ravandi, Amir

doi:10.1371/journal.pone.0195172

Cited by 26 publications

(33 citation statements)

References 51 publications

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“…Consistently to our observation of an increase of total 5(R,S)-5-F 2t -IsoP levels in the kidney 4 h after reperfusion and a decrease after 24 h (Fig. 4), in a rat model of unilateral IRI an increase of oxidized phosphatidylcholine species containing IsoP was observed 6 h after reperfusion which decreased after 24 h [53]. A similar time course of IsoP level was also observed in the liver of CCl 4 treated rats (see above) [7].…”

Section: Correlation Of Isopsupporting

confidence: 91%

“…Thus, here the applicability of the trans/cis-epoxy-PUFA ratio as oxidative stress marker cannot be evaluated based on comparison with IsoP levels. Even though IRI is linked to excess ROS formation [50,51] and an increase of oxidative damage derived IsoP following renal IRI has been observed in rat models [52,53], there are various factors influencing measured IsoP levels in this model. These include clamping time, since longer clamping seem to lead to higher IsoP levels [52], as well as the time point of sampling following reperfusion and the specimen analyzed, e.g.…”

Section: Correlation Of Isopmentioning

confidence: 94%

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Formation of trans-epoxy fatty acids correlates with formation of isoprostanes and could serve as biomarker of oxidative stress

Rund

Heylmann

Seiwert

et al. 2019

Prostaglandins & Other Lipid Mediators

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In mammals, epoxy-polyunsaturated fatty acids (epoxy-PUFA) are enzymatically formed from naturally occurring all-cis PUFA by cytochrome P450 monooxygenases leading to the generation of cis-epoxy-PUFA (mixture of R,S-and S,R-enantiomers). In addition, also non-enzymatic chemical peroxidation gives rise to epoxy-PUFA leading to both, cis-and trans-epoxy-PUFA (mixture of R,R-and S,S-enantiomers). Here, we investigated for the first time trans-epoxy-PUFA and the trans/cis-epoxy-PUFA ratio as potential new biomarker of lipid peroxidation. Their formation was analyzed in correlation with the formation of isoprostanes (IsoP), which are commonly used as biomarkers of oxidative stress. Five oxidative stress models were investigated including incubations of three human cell lines as well as the in vivo model Caenorhabditis elegans with tert-butyl hydroperoxide (t-BOOH) and analysis of murine kidney tissue after renal ischemia reperfusion injury (IRI). A comprehensive set of IsoP and epoxy-PUFA derived from biologically relevant PUFA (ARA, EPA and DHA) was simultaneously quantified by LC-ESI(-)-MS/ MS. Following renal IRI only a moderate increase in the kidney levels of IsoP and no relevant change in the trans/cis-epoxy-PUFA ratio was observed. In all investigated cell lines (HCT-116, HepG2 and Caki-2) as well as C. elegans a dose dependent increase of both, IsoP and the trans/cis-epoxy-PUFA ratio in response to the applied t-BOOH was observed. The different cell lines showed a distinct time dependent pattern consistent for both classes of autoxidatively formed oxylipins. Clear and highly significant correlations of the trans/cis-epoxy-PUFA ratios with the IsoP levels were found in all investigated cell lines and C. elegans. Based on this, we suggest the trans/cis-epoxy-PUFA ratio as potential new biomarker of oxidative stress, which warrants further investigation.

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Section: Correlation Of Isopsupporting

confidence: 91%

Section: Correlation Of Isopmentioning

confidence: 94%

Formation of trans-epoxy fatty acids correlates with formation of isoprostanes and could serve as biomarker of oxidative stress

Rund

Heylmann

Seiwert

et al. 2019

Prostaglandins & Other Lipid Mediators

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“…In atherosclerosis, blocking the action of OxPC with the antibody E06 in mice reduced the amount of atherosclerosis and aortic valve calcifications (39). Following renal ischemia reperfusion injury in rats, there was a significant elevation in 55 OxPC species which correlated with the severity of the injury (46). Recently, members of our team have identified OxPC in the airways of mice and humans following allergen challenge and these were shown to be correlated with PC 20 following allergen challenge in people.…”

Section: Epithelial Dysfunction and Disease Relevancementioning

confidence: 99%

Oxidized phosphatidylcholines induce multiple functional defects in airway epithelial cells

Pascoe

Roy

Turner-Brannen

et al. 2019

Preprint

Self Cite

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Oxidative stress is a hallmark of numerous airway diseases, contributing to extensive cell and tissue damage.Cell membranes and airway mucus are rich in phospholipids that are particularly susceptible to oxidative attack, producing a class of bioactive molecules known as oxidized phosphatidylcholines (OxPC). With the recent discovery of elevated OxPC levels in animal models of asthma and asthmatic patients, we hypothesized that OxPC could directly contribute to this disease by inducing airway epithelial cell dysfunction.We found that OxPC induced dose-dependent cell stress and loss of viability in a range of epithelial cell types.These responses corresponded with significant epithelial barrier dysfunction, which was further compounded when combining OxPC with an epithelial wound. Sub-lethal doses of OxPC were seen to significantly inhibit DNA synthesis and migration required for wound healing, but cells could recover if OxPC were washed off soon after treatment. OxPC induced extensive generation of reactive oxygen species that could not be abrogated by known OxPC receptor blockers, and caused extensive lipid peroxidation that could only be partially inhibited by the antioxidant n-acetyl cysteine. This raises the possibility that OxPC specifically cause pathological lipid metabolism, in a self-propagating cycle that contributes to disease pathogenesis.In summary, we have identified OxPC as a bioactive model that significantly impairs multiple facets of epithelial cell function, consistent with pathological features of asthmatic epithelium. Further characterisation of the mechanisms by which OxPC affect epithelial cells could yield new insights into how oxidative stress contributes to the pathogenesis of airway disease.

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“…Renal tissue pathology can directly reflect the degree of renal tissue damage and the location of lesions (Solati et al, 2018). HE staining showed renal tubular epithelial cell degeneration, water-like lesions, infiltration of inflammatory cells around the renal tubules, interstitial cells, and partial apoptosis in the IR group; interstitial oedema in the UCP2 À/À þIR group was greater than that in the IR group.…”

Section: Ucp2 Alleviates Renal Tissue Injurymentioning

confidence: 99%

“…In addition, renal tubular epithelial cells are damaged, and apoptosis and necrosis occur in severe cases. There is growing evidence that reactive oxygen species (ROS) in renal tubular epithelial cells are the main cause of IRI; oxidative stress theory demonstrates that ROS are produced in the renal tissue due to the ischaemia and reperfusion state, and ROS are thought to be minuscule molecules such as the superoxide anion (O À2 ), hydroxyl radicals ( -OH) and hydroperoxides (H 2 O 2 ), which are mainly produced in mitochondria; this leads to lipid peroxidation, inflammatory reactions and apoptosis (Moniruzzaman et al, 2018;Simon et al 2000;Solati et al, 2018). Mitochondrial membrane potential has been linked to apoptosis and inflammation of IRI (Ji et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Uncoupling protein 2 prevents ischaemia reperfusion injury through the regulation ROS/NF-κB signalling in mice

Zhang¹,

Guo²,

Li³

et al. 2019

Molecular Membrane Biology

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Background and objective: Renal ischaemia reperfusion injury (IRI), characterized by excessive cell apoptosis and inflammation, remains a clinical challenge. Mitochondrial membrane potential is related to apoptosis and inflammation of IRI. Previous studies have indicated that uncoupling protein 2 (UCP2) and its receptors play an important role in inflammation, apoptosis and injuries, especially in oxidative stress injury. However, the underlying mechanisms of UCP2 in IRI are still not fully understood. Methods and results: In the present study, male C57 mice were randomly divided into three groups:sham, IR, and UCP2-/-+IR. The IRI model was established by removing the right kidney and clamping the left kidney for 45 min followed by reperfusion. Blood urea nitrogen (BUN) and creatinine were higher in UCP2-/-+IR mouse serum than in IR mouse serum. In addition, relative to the IR group, UCP2-/-+IR mouse renal cells had increased reactive oxygen species (ROS) production, aggravating tissue damage. We examined changes in the NFjB pathway and found that after UCP2 knockdown, IjB and IKK phosphorylation increased, and nuclear NFjB increased, which stimulated inflammation. Moreover, there was an increase in apoptosis in the UCP2-/-+IR group. Conclusion: UCP2 can prevent IRI in C57 mice. Mechanistically, UCP2 may decrease ROS expression, NFjB activation and caspase-3 cleavage, rendering UCP2 a potential therapeutic target against IRI.

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Oxidized phosphatidylcholines are produced in renal ischemia reperfusion injury

Cited by 26 publications

References 51 publications

Formation of trans-epoxy fatty acids correlates with formation of isoprostanes and could serve as biomarker of oxidative stress

Formation of trans-epoxy fatty acids correlates with formation of isoprostanes and could serve as biomarker of oxidative stress

Oxidized phosphatidylcholines induce multiple functional defects in airway epithelial cells

Uncoupling protein 2 prevents ischaemia reperfusion injury through the regulation ROS/NF-κB signalling in mice

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