Detection and Biological Activities of Carboxyethylpyrrole Ethanolamine Phospholipids (CEP-EPs)

Wang, Hua; Guo, Junhong; West, Xiaoxia Z.; Bid, Hemant K.; Liang, Lu; Li, Hong; Jang, Geeng-Fu; Zhang, Lei; Crabb, John W.; Genomic, Clinical; Linetsky, Mikhail; Salomon, Robert G.

doi:10.1021/tx500216a

Cited by 28 publications

(60 citation statements)

References 28 publications

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“…Although the biological activities and role of such derivatives in vivo have been widely studied for the past 3 decades, 7,8 studies of similar derivatives of phosphatidylethanolamine are very limited to date. 6,11 Evidence supports the notion that a variety of PE adducts and derivatives may form during conditions of oxidative stress in vivo. 9,11,32 Moreover, recent in vitro studies have shown that PE is the preferred target for modification by some lipid aldehydes.…”

Section: Discussionmentioning

confidence: 67%

“…6,11 Evidence supports the notion that a variety of PE adducts and derivatives may form during conditions of oxidative stress in vivo. 9,11,32 Moreover, recent in vitro studies have shown that PE is the preferred target for modification by some lipid aldehydes. 10 However, the biological activities of such adducts and/or derivatives have just recently attracted attention and cellular receptors recognizing them are not known.…”

Section: Discussionmentioning

confidence: 67%

“…They were synthesized as described 11 (supplemental Figures 1 and 2) and tested in several platelet activation assays. CAP-PEs induced significant P-selectin expression ( Figure 1A-B) and integrin a IIb b 3 activation ( Figure 1C-D) in isolated human platelets.…”

Section: Cap-pes Induce Platelet Activationmentioning

confidence: 99%

“…10 Carboxyalkylpyrrole-PE derivatives (CAP-PEs) were recently detected in human blood. 11 However, whether CAP-PEs accumulate in circulation in dyslipidemia, whether they can affect the function of platelets and thrombosis, and what the receptors and signaling pathways in platelets implicated by the novel derivatives is not known.…”

Section: Introductionmentioning

confidence: 99%

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Novel phosphatidylethanolamine derivatives accumulate in circulation in hyperlipidemic ApoE−/− mice and activate platelets via TLR2

Biswas

Liang

Panigrahi

et al. 2016

Blood

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Section: Discussionmentioning

confidence: 67%

Section: Discussionmentioning

confidence: 67%

Section: Cap-pes Induce Platelet Activationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Novel phosphatidylethanolamine derivatives accumulate in circulation in hyperlipidemic ApoE−/− mice and activate platelets via TLR2

Biswas

Liang

Panigrahi

et al. 2016

Blood

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“…5G). Furthermore, C22:6 LPE and related metabolites can be oxidized to form 2-ω-carboxyethyl pyrrole (CEP) protein derivatives (34), whose levels were higher in the photoreceptor cell inner and outer segments and RPE of HG than in LG and HGxoLG mice (Fig. 4 I and J).…”

Section: Resultsmentioning

confidence: 99%

Involvement of a gut–retina axis in protection against dietary glycemia-induced age-related macular degeneration

Rowan

Jiang

Korem

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

201

192

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Age-related macular degeneration (AMD) is the major cause of blindness in developed nations. AMD is characterized by retinal pigmented epithelial (RPE) cell dysfunction and loss of photoreceptor cells. Epidemiologic studies indicate important contributions of dietary patterns to the risk for AMD, but the mechanisms relating diet to disease remain unclear. Here we investigate the effect on AMD of isocaloric diets that differ only in the type of dietary carbohydrate in a wild-type aged-mouse model. The consumption of a high-glycemia (HG) diet resulted in many AMD features (AMDf), including RPE hypopigmentation and atrophy, lipofuscin accumulation, and photoreceptor degeneration, whereas consumption of the lower-glycemia (LG) diet did not. Critically, switching from the HG to the LG diet late in life arrested or reversed AMDf.LG diets limited the accumulation of advanced glycation end products, long-chain polyunsaturated lipids, and their peroxidation end-products and increased C3-carnitine in retina, plasma, or urine. Untargeted metabolomics revealed microbial cometabolites, particularly serotonin, as protective against AMDf. Gut microbiota were responsive to diet, and we identified microbiota in the Clostridiales order as being associated with AMDf and the HG diet, whereas protection from AMDf was associated with the Bacteroidales order and the LG diet. Network analysis revealed a nexus of metabolites and microbiota that appear to act within a gut-retina axis to protect against diet-and age-induced AMDf. The findings indicate a functional interaction between dietary carbohydrates, the metabolome, including microbial cometabolites, and AMDf. Our studies suggest a simple dietary intervention that may be useful in patients to arrest AMD.age-related macular degeneration | glycemic index | advanced glycation end-product | gut microbiome | metabolomics A ge-related macular degeneration (AMD) is the leading cause of irremediable blindness in the industrialized world, with 200 million cases projected by 2020, at a cost of $300 billion (1, 2). Dry AMD accounts for the great majority of cases and is associated with photoreceptor cell loss, often preceded by compromise to the retina pigment epithelium (RPE) cells that nourish and remove waste from the photoreceptors. The etiology of AMD remains an enigma but is clearly multifactorial. Stresses associated with AMD include environment, age, and genetics (3). Frustratingly, there are no early biomarkers to anticipate AMD, and there are no therapies or cure.Recently, we and others observed in epidemiologic studies that, in addition to micronutrients (4-6), macronutrient quality [e.g., consuming a diet with a high glycemic index (GI)] is a significant risk factor for AMD onset and/or progress in nondiabetic humans (7)(8)(9). The GI appears to be an attractive dietary intervention target, because simple replacement of small amounts of high-index foods (such as white bread) with lower-index foods (such as wholegrain bread) can significantly reduce glycemic peaks without requiring ...

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Biological and pathophysiological roles of end-products of DHA oxidation

Yakubenko

Byzova

2017

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

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Background Polyunsaturated fatty acids (PUFA) are known to be present and/or enriched in vegetable and fish oils. Among fatty acids, n-3 PUFA are generally considered to be protective in inflammation-related diseases. The guidelines for substituting saturated fatty acids for PUFAs have been highly publicized for decades by numerous health organizations. Recently, however, the beneficial properties of n-3 PUFA are questioned by detailed analyses of multiple randomized controlled clinical trials. The reported heterogeneity of results is likely due not only to differential effects of PUFAs on various pathological processes in humans, but also to the wide spectrum of PUFA's derived products generated in vivo. Scope of review The goal of this review is to discuss the studies focused on well-defined end-products of PUFAs oxidation, their generation, presence in various pathological and physiological conditions, their biological activities and known receptors. Carboxyethylpyrrole (CEP), a DHA-derived oxidized product, is especially emphasized due to recent data demonstrating its pathophysiological significance in many inflammation-associated diseases, including atherosclerosis, hyperlipidemia, thrombosis, macular degeneration, and tumor progression. Major conclusions CEP is a product of radical-based oxidation of PUFA that forms adducts with proteins and lipids in blood and tissues, generating new powerful ligands for TLRs and scavenger receptors. The interaction of CEP with these receptors affects inflammatory response, angiogenesis, and wound healing. General Significance The detailed understanding of CEP–mediated cellular responses may provide a basis for the development of novel therapeutic strategies and dietary recommendations.

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Detection and Biological Activities of Carboxyethylpyrrole Ethanolamine Phospholipids (CEP-EPs)

Cited by 28 publications

References 28 publications

Novel phosphatidylethanolamine derivatives accumulate in circulation in hyperlipidemic ApoE−/− mice and activate platelets via TLR2

Novel phosphatidylethanolamine derivatives accumulate in circulation in hyperlipidemic ApoE−/− mice and activate platelets via TLR2

Involvement of a gut–retina axis in protection against dietary glycemia-induced age-related macular degeneration

Biological and pathophysiological roles of end-products of DHA oxidation

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