ArticleJournal of lipid research2013
Posttranslational modification by an isolevuglandin diminishes activity of the mitochondrial cytochrome P450 27A1.
Article in Journal of lipid research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
14 citing papers in PubMed, 20 citations in OpenAlex.
- Challenges and Opportunities in P450 Research on the Eye.Drug metabolism and disposition: the biological fate of chemicals · 2023Review
- Mass spectrometry-based retina proteomics.Mass spectrometry reviews · 2023Review
- Aberrant Cholesterol Metabolic Genes Regulation in a Negative Feedback Loop Induced by an Alphacoronavirus.Frontiers in nutrition · 2022Article
- Isolevuglandins as mediators of disease and the development of dicarbonyl scavengers as pharmaceutical interventions.Pharmacology & therapeutics · 2020Review
- Drugs and Scaffold That Inhibit Cytochrome P450 27A1 In Vitro and In Vivo.Molecular pharmacology · 2018Article
- Total Synthesis Confirms the Molecular Structure Proposed for Oxidized Levuglandin DJournal of natural products · 2017Article
- 4-Hydroxy-7-oxo-5-heptenoic Acid Lactone Induces Angiogenesis through Several Different Molecular Pathways.Chemical research in toxicology · 2016Article
- Molecular Structures of Isolevuglandin-Protein Cross-Links.Chemical research in toxicology · 2016Article
- Marketed Drugs Can Inhibit Cytochrome P450 27A1, a Potential New Target for Breast Cancer Adjuvant Therapy.Molecular pharmacology · 2015Article
- Isolevuglandin adducts in disease.Antioxidants & redox signaling · 2015Review
- Mass spectrometry detection of isolevuglandin adduction to specific protein residues.Methods in molecular biology (Clifton, N.J.) · 2015Article
- Lipid peroxidation generates biologically active phospholipids including oxidatively N-modified phospholipids.Chemistry and physics of lipids · 2014Review
- Cholesterol in the retina: the best is yet to come.Progress in retinal and eye research · 2014Review
- Pretreatment with pyridoxamine mitigates isolevuglandin-associated retinal effects in mice exposed to bright light.The Journal of biological chemistry · 2013Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Posttranslational modification by isolevuglandins (isoLGs), arachidonate oxidation products, is an important yet understudied process associated with altered protein properties. This type of modification is detected in cytochrome P450 27A1 (CYP27A1), a multifunction enzyme expressed in almost every cell and involved in the metabolism of cholesterol and other sterols. Previously, the CYP27A1 Lys(358)-isoLG adduct was found in human retina afflicted with age-related macular degeneration. Yet, the effect of Lys(358) modification on enzyme activity was not investigated. Herein, we characterized catalytic properties of Lys(358) as well as Lys(476) CYP27A1 mutants before and after isoLG treatment and quantified the extent of modification by multiple reaction monitoring. The K358R mutant was less susceptible to isoLG-induced loss of catalytic activity than the wild type (WT), whereas the K476R mutant was nearly as vulnerable as the WT. Both mutants showed less isoLG modification than WT. Thus, modification of Lys(358), a residue involved in redox partner interactions, is the major contributor to isoLG-associated loss of CYP27A1 activity. Our data show the specificity of isoLG modification, provide direct evidence that isoLG adduction impairs enzyme activity, and support our hypothesis that isoLG modification in the retina is detrimental to CYP27A1 enzyme activity, potentially disrupting cholesterol homeostasis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.