ArticleThe Journal of biological chemistry2011
Phosphatidylethanolamines modified by γ-ketoaldehyde (γKA) induce endoplasmic reticulum stress and endothelial activation.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 52 citations in OpenAlex.
- Article
- Glycerophospholipids in Red Blood Cells Are Associated with Aerobic Performance in Young Swimmers.Nutrients · 2024Article
- Serum Isolevuglandin IgG Antibody Concentrations Are Increased in Patients with Systemic Lupus Erythematosus and Associated with Lower 24-Hour Blood Pressure.Frontiers in lupus · 2024Article
- Altered Functionality of Lipoprotein(a) Impacts on Angiogenesis in Diabetic Retinopathy.Investigative ophthalmology & visual science · 2023Article
- PLIN2 Mediates Neuroinflammation and Oxidative/Nitrosative Stress via Downregulating Phosphatidylethanolamine in the Rostral Ventrolateral Medulla of Stressed Hypertensive Rats.Journal of inflammation research · 2021Article
- Mitochondrial Isolevuglandins Contribute to Vascular Oxidative Stress and Mitochondria-Targeted Scavenger of Isolevuglandins Reduces Mitochondrial Dysfunction and Hypertension.Hypertension (Dallas, Tex. : 1979) · 2020Article
- A Comprehensive Review on Source, Types, Effects, Nanotechnology, Detection, and Therapeutic Management of Reactive Carbonyl Species Associated with Various Chronic Diseases.Antioxidants (Basel, Switzerland) · 2020Review
- Cadmium-Induced Oxidative Stress: Focus on the Central Nervous System.Antioxidants (Basel, Switzerland) · 2020Review
- The Implications for Cells of the Lipid Switches Driven by Protein-Membrane Interactions and the Development of Membrane Lipid Therapy.International journal of molecular sciences · 2020Review
- Isolevuglandins as mediators of disease and the development of dicarbonyl scavengers as pharmaceutical interventions.Pharmacology & therapeutics · 2020Review
- Cardiolipin, Perhydroxyl Radicals, and Lipid Peroxidation in Mitochondrial Dysfunctions and Aging.Oxidative medicine and cellular longevity · 2020Review
- The Role of Phosphatidylethanolamine Adducts in Modification of the Activity of Membrane Proteins under Oxidative Stress.Molecules (Basel, Switzerland) · 2019Review
- Modification by isolevuglandins, highly reactive γ-ketoaldehydes, deleteriously alters high-density lipoprotein structure and function.The Journal of biological chemistry · 2018Article
- Reactive Carbonyl Species Scavengers-Novel Therapeutic Approaches for Chronic Diseases.Current pharmacology reports · 2017Article
- Detection of atherosclerotic plaques in ApoE-deficient mice using (99m)Tc-duramycin.Nuclear medicine and biology · 2016Article
- Efficient Quantitative Analysis of Carboxyalkylpyrrole Ethanolamine Phospholipids: Elevated Levels in Sickle Cell Disease Blood.Chemical research in toxicology · 2016Article
- Article
- Structural, biological and biophysical properties of glycated and glycoxidized phosphatidylethanolamines.Free radical biology & medicine · 2016Article
- Clinical Relevance of Biomarkers of Oxidative Stress.Antioxidants & redox signaling · 2015Review
- Isolevuglandin-type lipid aldehydes induce the inflammatory response of macrophages by modifying phosphatidylethanolamines and activating the receptor for advanced glycation endproducts.Antioxidants & redox signaling · 2015Article
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Peroxidation of plasma lipoproteins has been implicated in the endothelial cell activation and monocyte adhesion that initiate atherosclerosis, but the exact mechanisms underlying this activation remain unclear. Lipid peroxidation generates lipid aldehydes, including the γ-ketoaldehydes (γKA), also termed isoketals or isolevuglandins, that readily modify the amine headgroup of phosphatidylethanolamine (PE). We hypothesized that aldehyde modification of PE could mediate some of the proinflammatory effects of lipid peroxidation. We found that PE modified by γKA (γKA-PE) induced THP-1 monocyte adhesion to human umbilical cord endothelial cells. γKA-PE also induced expression of adhesion molecules and increased MCP-1 and IL-8 mRNA in human umbilical cord endothelial cells. To determine the structural requirements for γKA-PE activity, we tested several related compounds. PE modified by 4-oxo-pentanal induced THP-1 adhesion, but N-glutaroyl-PE and C(18:0)N-acyl-PE did not, suggesting that an N-pyrrole moiety was essential for cellular activity. As the N-pyrrole headgroup might distort the membrane, we tested the effect of the pyrrole-PEs on membrane parameters. γKA-PE and 4-oxo-pentanal significantly reduced the temperature for the liquid crystalline to hexagonal phase transition in artificial bilayers, suggesting that these pyrrole-PE markedly altered membrane curvature. Additionally, fluorescently labeled γKA-PE rapidly internalized to the endoplasmic reticulum (ER); γKA-PE induced C/EBP homologous protein CHOP and BiP expression and p38 MAPK activity, and inhibitors of ER stress reduced γKA-PE-induced C/EBP homologous protein CHOP and BiP expression as well as EC activation, consistent with γKA-PE inducing ER stress responses that have been previously linked to inflammatory chemokine expression. Thus, γKA-PE is a potential mediator of the inflammation induced by lipid peroxidation.
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Registered trials
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