Incorporation and distribution of epoxyeicosatrienoic acids into cellular phospholipids.

Bernström, Kerstin; Kayganich, Kathleen; Murphy, R.C.; Fitzpatrick, Francis A.

doi:10.1016/s0021-9258(19)50579-8

Cited by 65 publications

(9 citation statements)

References 44 publications

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“…Nonpolar eicosanoids are not only present in the in¯ammatory lesions as a free form but also tend to esterify in cell phospholipids, which results in large amounts of monohydroxy fatty acids esteri®ed into cell phospholipids in in¯ammatory lesions (Baer et al, 1991;Ku Èhn et al, 1992). Indeed, among the eicosanoids and octadecanoids only the hydroxy and epoxy derivatives have been reported to be incorporated into cellular phospholipids (Stenson and Parker, 1979;Schade et al, 1987;Brezinski and Serhan, 1990;Wang et al, 1990;Brinkman et al, 1991;Bernstrom et al, 1992). Here we report that HxB 3 is also present in psoriatic lesions esteri®ed in the phospholipids in an HxB 3 :12-HETE ratio of 0.19 after both alkaline saponi®cation and PLA 2 -catalyzed hydrolysis.…”

Section: Discussionmentioning

confidence: 60%

Hepoxilin B3 and its Enzymatically Formed Derivative Trioxilin B3 are Incorporated into Phospholipids in Psoriatic Lesions

Antón

Camacho

Puig

et al. 2002

Journal of Investigative Dermatology

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In previous studies we observed that normal human epidermis forms 12-oxo-eicosatetraenoic acid (12-oxo-ETE) and hepoxilin B3 (HxB3) as major eicosanoids, both being elevated in psoriasis. We also observed that normal epidermis, in a reaction probably catalyzed by 12-lipoxygenase, only synthesize one of the two possible 10-hydroxy epimers of HxB3. We have now extended these previous studies investigating further transformation of HxB3 into trioxilin B3 (TrXB3) and esterification of both into phospholipids. Phospholipids were extracted from normal epidermis and from psoriatic scales. A combination of high performance liquid chromatography and gas chromatography-mass spectrometry analysis demonstrated the occurrence of HxB3 and TrXB3 in the phospholipids of psoriatic lesions. Alkaline- and phospholipase-A2-mediated hydrolysis of the phospholipids yielded similar quantities of both HxB3 and TrXB3 indicating their preference for the sn-2 position of glycerophospholipids. The thin layer chromatography analysis of the phospholipid classes after incubation of epidermal cells with [14C]-labeled HxB3, TrXB3, 12-hydroxy-eicosatetraenoic acid (12-HETE), 12-oxo-ETE, or 15-HETE showed that 12-HETE was the most esterified (12-HETE >15-HETE > TrXB3 > 12-oxo-ETE > HxB3). HxB3 and TrXB3 were mainly esterified in phosphatidyl-choline and phosphatidyl-ethanolamine. HxB3 was also enzymatically converted into TrXB3 in vitro. HxB3 epoxide hydrolase-like activity was not observed when boiled tissue was incubated with [14C]-HxB3, this activity being located in the cytosol fraction (100,000 x g supernatant) of fresh tissue. These findings suggest that in vivo some part of HxB3 is transformed into TrXB3 and both compounds are partially incorporated into the phospholipids.

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Section: Discussionmentioning

confidence: 60%

Hepoxilin B3 and its Enzymatically Formed Derivative Trioxilin B3 are Incorporated into Phospholipids in Psoriatic Lesions

Antón

Camacho

Puig

et al. 2002

Journal of Investigative Dermatology

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“…They have putative GPCR mechanisms although they may act indirectly to influence ion channel proteins or the membranes in which they reside. Typically, as is the case with EpFA, they are tightly regulated by the activity of regulating enzymes that degrade them or reincorporate them into membranes [13,14]. Some lipids such as AEA and a few EpFA that conform to the structural requirements of TRP lipid agonism also have been demonstrated to additionally activate TRP channels [10,15].…”

Section: Pain Sensation and Lipidsmentioning

confidence: 99%

Soluble Epoxide Hydrolase Regulation of Lipid Mediators Limits Pain

et al. 2020

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The role of lipids in pain signaling is well established and built on decades of knowledge about the pain and inflammation produced by prostaglandin and leukotriene metabolites of cyclooxygenase and lipoxygenase metabolism, respectively. The analgesic properties of other lipid metabolites are more recently coming to light. Lipid metabolites have been observed to act directly at ion channels and G protein-coupled receptors on nociceptive neurons as well as act indirectly at cellular membranes. Cytochrome P450 metabolism of specifically long-chain fatty acids forms epoxide metabolites, the epoxy-fatty acids (EpFA). The biological role of these metabolites has been found to mediate analgesia in several types of pain pathology. EpFA act through a variety of direct and indirect mechanisms to limit pain and inflammation including nuclear receptor agonism, limiting endoplasmic reticulum stress and blocking mitochondrial dysfunction. Small molecule inhibitors of the soluble epoxide hydrolase can stabilize the EpFA in vivo, and this approach has demonstrated relief in preclinical modeled pain pathology. Moreover, the ability to block neuroinflammation extends the potential benefit of targeting soluble epoxide hydrolase to maintain EpFA for neuroprotection in neurodegenerative disease.

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“…These findings agreed with older reports using other PLA 2 s and different methodology (Sevanian et al, 1981; Van den Berg et al, 1993). Furthermore, Bernstrom et al (1992) reported that EET stereoisomers are readily incorporated into cellular phospholipids and are released at rates exceeding those observed for arachidonic acid, at least in the case of 14,15‐EET. Clearly, our data with the products of CYP‐450 differ from those obtained with the 15‐lipoxygenase, as well as from those reported for the stereoisomers.…”

Section: Discussionmentioning

confidence: 99%

Hydrolysis of glycerophosphocholine epoxides by human group IIA, V, and X secretory phospholipases A₂

Kuksis

Pruzanski

2021

Lipids

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This study was prompted by recent reports that epoxyeicosatrienoic (EET) and epoxyeicosatetraenoic (EEQ) acids accelerate tumor growth and metastasis by stimulation of angiogenesis, while eicosapentaenoic (EPA) and epoxydocosapentaenoic (EDP) acids inhibit angiogenesis, tumor growth, and metastasis. Cytochrome P450 epoxygenases convert arachidonic to EET, eicosapentaenoic acid to EEQ, and docosahexaenoic acid to EDP, which are found both in free form and esterified to glycerophosphocholine (GPC). Both free and esterified epoxy (EP) acids are also formed during lipid autoxidation. For biological activity, the GPC-EP requires hydrolysis, which we presumed could occur by sPLA 2 s located in proximity of lipoproteins carrying the lipid epoxides. The plasma lipoproteins were isolated by ultracentrifugation and analyzed by LC/ESI-MS. The GPC-EPs were identified by reference to standards and to retention times of phospholipid masses. The GPC-EP monoepoxides (corrected for isobaric ether overlaps) in stored human LDL, HDL, HDL 3 , or APHDL ranged from 0 to 1 nmol/mg protein, but during 4-h incubation at 37 C increased to 1-5 nmol/mg protein. An incubation of autoxidized LDL, HDL, or HDL 3 with 1 μg/ml of group V or X sPLA 2 resulted in complete hydrolysis of diacyl GPC epoxide esters. Group IIA sPLA 2 at 1 μg/ml failed to produce significant hydrolysis in 4 h, but at 2.5 μg/ml in 8 h yielded almost 80% hydrolysis, which represented complete diacyl GPC-EP hydrolysis. The present study shows that group IIA, V, and X sPLA 2 s are capable of extensive hydrolysis of PtdCho epoxides of autoxidized plasma lipoproteins. Therefore, all three human sPLA 2 s were potentially capable of inducing epoxide biological activity in vivo.

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Incorporation and distribution of epoxyeicosatrienoic acids into cellular phospholipids.

Cited by 65 publications

References 44 publications

Hepoxilin B3 and its Enzymatically Formed Derivative Trioxilin B3 are Incorporated into Phospholipids in Psoriatic Lesions

Hepoxilin B3 and its Enzymatically Formed Derivative Trioxilin B3 are Incorporated into Phospholipids in Psoriatic Lesions

Soluble Epoxide Hydrolase Regulation of Lipid Mediators Limits Pain

Hydrolysis of glycerophosphocholine epoxides by human group IIA, V, and X secretory phospholipases A₂

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Incorporation and distribution of epoxyeicosatrienoic acids into cellular phospholipids.

Cited by 65 publications

References 44 publications

Hepoxilin B3 and its Enzymatically Formed Derivative Trioxilin B3 are Incorporated into Phospholipids in Psoriatic Lesions

Hepoxilin B3 and its Enzymatically Formed Derivative Trioxilin B3 are Incorporated into Phospholipids in Psoriatic Lesions

Soluble Epoxide Hydrolase Regulation of Lipid Mediators Limits Pain

Hydrolysis of glycerophosphocholine epoxides by human group IIA, V, and X secretory phospholipases A2

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Hydrolysis of glycerophosphocholine epoxides by human group IIA, V, and X secretory phospholipases A₂