Article
Genetics & Heredity
Alrun Hotz, Julia Kopp, Emmanuelle Bourrat, Vinzenz Oji, Katalin Komlosi, Kathrin Giehl, Bakar Bouadjar, Anette Bygum, Iliana Tantcheva-Poor, Maritta Hellstrom Pigg, Cristina Has, Zhou Yang, Alan D. Irvine, Regina C. Betz, Giovanna Zambruno, Gianluca Tadini, Kira Suessmuth, Robert Gruber, Matthias Schmuth, Juliette Mazereeuw-Hautier, Natalie Jonca, Sophie Guez, Michela Brena, Angela Hernandez-Martin, Peter van den Akker, Maria C. Bolling, Katariina Hannula-Jouppi, Andreas D. Zimmer, Svenja Alter, Anders Vahlquist, Judith Fischer
Summary: ARCI is a group of non-syndromic cornification disorders that includes several types of ichthyoses. Mutations in ALOX12B and ALOXE3 genes are identified to cause ARCI, leading to varying phenotypes. The distribution and potential hotspots of mutations in ALOX12B and ALOXE3 may influence the severity of the disease.
Article
Dermatology
L. Hake, K. Suessmuth, K. Komlosi, J. Kopp, C. Drerup, D. Metze, H. Traupe, I Hausser, K. M. Eckl, H. C. Hennies, J. Fischer, V Oji
Summary: This study aims to further delineate the clinical spectrum of self-improving congenital ichthyosis (SICI), a subtype of autosomal-recessive congenital ichthyosis (ARCI), and its impact on quality of life (QoL). The study found that SICI patients often have hypo-/anhidrosis and insufficient vitamin D levels. They also exhibit features such as brachydactyly and kinking of the ears. QoL is less impaired in patients under the age of 16, regardless of ARCI type.
JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY
(2022)
Article
Immunology
Stanzin Dawa, Dilip Menon, Prabhakar Arumugam, Akash Kumar Bhaskar, Moumita Mondal, Vivek Rao, Sheetal Gandotra
Summary: Lipid metabolism plays a crucial role in the interaction between host and pathogen during Mycobacterium tuberculosis infection. The accumulation of triglyceride in necrotic granulomas is important for the success of the pathogen, and manipulating lipid droplet homeostasis may potentially offer a new approach for host-directed therapy in Tuberculosis.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Tianshu Wu, Xinyu Wang, Min Chen, Xiaomeng Zhang, Jixiang Zhang, Xuqing Fan, Yunbo Yu, Wenxin Zheng, Supu Maitiyv, Yan Wang, Lu Kong, Meng Tang
Summary: Recently, there has been growing interest in the application of graphene quantum dots (GQDs), but the lack of information on their risk assessments could hinder their contributions in neuroscience. This study found that the intranasal administration of amino group functionalized GQDs (A-GQDs) increased neuronal cell death, triggered ferroptosis activities, and caused inflammatory reactions in the hippocampus. Similar adverse effects were observed in BV2 microglial cells treated with A-GQDs, which were attenuated by a ferroptosis-specific inhibitor. The findings highlight the importance of risk assessments and provide toxic biomarkers for the interventions of GQDs in the brain.
Article
Cell Biology
Yifei Qin, Zhuo Pei, Zhuan Feng, Peng Lin, Shijie Wang, Yong Li, Fei Huo, Quancheng Wang, Zhiping Wang, Zhi-Nan Chen, Jiao Wu, Yi-Fei Wang
Summary: YAP signaling plays a crucial role in regulating ferroptotic cell death, with its activation significantly increasing sensitivity of hepatocellular carcinoma cells to ferroptosis. Furthermore, the study found that YAP promotes ferroptosis through targeting the gene ALOXE3. Therefore, pathogenic alterations in the YAP signaling pathway may serve as biomarkers to predict cancer cell responsiveness to future ferroptosis-inducing therapies.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Genetics & Heredity
Yonggyun Kim, David Stanley
Summary: This paper focuses on eicosanoid signaling in insect immunology, detailing the biosynthesis, pathways, and roles in immune responses. The newly discovered insect PGs play a significant role in understanding insect immune system.
Article
Immunology
Miltan Chandra Roy, Shabbir Ahmed, Yonggyun Kim
Summary: Various microbiota reside in the insect gut, but infections of pathogens can disrupt this balance. A protein called DSP1 is released into the plasma upon nematode infection, and activates PLA(2). Activated PLA(2) leads to an increase in PGE(2) levels, which in turn up-regulates Ca2+ signal and increases ROS production to protect the beneficial microflora and gut epithelium.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Kishore K. Joshi, Tarmie L. Matlack, Stephanie Pyonteck, Mehul Vora, Ralph Menzel, Christopher Rongo
Summary: Metazoans utilize protein homeostasis pathways to respond to adverse conditions, with the nervous system playing a role in regulating proteostasis in different tissues. This study reveals that Caenorhabditis elegans uses biogenic amine neurotransmitters to modulate UPS proteostasis in epithelia by promoting eicosanoid production through P450 monooxygenases, ultimately maintaining protein turnover.
Article
Oncology
Xinzhi Yang, Jiangang Liu, Chenci Wang, Kenneth King-yip Cheng, Hongchao Xu, Qingzhong Li, Tian Hua, Xue Jiang, Lili Sheng, Jie Mao, Zhuohao Liu
Summary: The study demonstrates that down-regulation of ALOXE3 in glioblastoma may contribute to resistance to ferroptosis and enhanced migration of cancer cells. Furthermore, miR-18a directly targets ALOXE3 to suppress its functions in glioblastoma cells, indicating potential for targeting the miR-18a/ALOXE3 axis as a therapeutic approach for glioblastoma treatment.
Article
Biochemistry & Molecular Biology
JuDong Yeo, Christopher C. Parrish
Summary: Shotgun lipidomics was used to identify and quantify phospholipids in salmon muscle tissue, focusing on omega-3 fatty acids distribution and eicosanoids. 43 PL species were identified, with 16:0-22:6 PtdCho being predominant. Additionally, prostaglandin E2 and prostaglandin F3 alpha were identified for the first time in salmon muscle.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Neurosciences
Mei-Mei Gao, Hao-Ying Huang, Si-Yu Chen, Hui-Ling Tang, Na He, Wen-Cai Feng, Ping Lu, Fei Hu, Hua-Juan Yan, Yue-Sheng Long
Summary: This study identified ALOXE3 gene mutations in epilepsy patients and found that some variants may lead to reduced enzyme activity, potentially contributing to epileptogenesis. The research suggests a novel avenue for clinical diagnosis of epilepsy by understanding the relationship between ALOXE3 mutations and the pathogenesis of epilepsy.
BRAIN RESEARCH BULLETIN
(2021)
Article
Biochemistry & Molecular Biology
Joseph D. Ho, Matthew R. Lee, Charles T. Rauch, Kristen Aznavour, Jonathan S. Park, John G. Luz, Stephen Antonysamy, Bradley Condon, Milan Maletic, Aiping Zhang, Michael J. Hickey, Norman E. Hughes, Srinivasan Chandrasekhar, Ashley Sloan, Karen Gooding, Anita Harvey, Xiao-Peng Yu, Steven D. Kahl, Bryan H. Norman
Summary: The research focused on inhibiting the formation of both PGs and LTs by generating ligand-protein X-ray crystal structures and using molecular modeling and structure-based drug design (SBDD) to identify hybrid structures. Compounds 4 and 5 were synthesized and showed potent in vitro inhibition of both targets, offering insights into potential dual inhibitors for these important integral membrane protein drug targets.
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
(2021)
Review
Biochemistry & Molecular Biology
Siva S. R. Iyer, Mollie K. Lagrew, Stephanie M. Tillit, Ramak Roohipourmoallai, Samuel Korntner
Summary: Diabetic retinopathy is a leading cause of blindness worldwide, with the vitreous humor serving as a complex interactive platform for cytokines in the diabetic eye. Recent research has made significant progress in understanding the molecular patho-mechanisms of this disease through studying growth factors, cytokines, chemokines, and lipid-derived metabolites in the vitreous.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Immunology
Johanna von Gerichten, Annette L. West, Nicola A. Irvine, Elizabeth A. Miles, Philip C. Calder, Karen A. Lillycrop, Graham C. Burdge, Barbara A. Fielding
Summary: Immune function changes with age, and oxylipin synthesis might mediate these changes. This study investigated the impact of essential fatty acid (EFA) ratio on oxylipin secretion by T cells and whether this changes across life stages. The results showed that the EFA ratio influenced the extracellular oxylipin profile more than mitogen stimulation, and fetal T cells had higher oxylipin concentrations compared to adult and senior T cells. The capacity of T cells to synthesize oxylipins might contribute to their immunological phenotype.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Multidisciplinary Sciences
Hui Jing, Alex Reed, Olesya A. Ulanovskaya, Jan-Sebastian Grigoleit, Dylan M. Herbst, Cassandra L. Henry, Haoxin Li, Sabrina Barbas, Jason Germain, Kim Masuda, Benjamin F. Cravatt
Summary: Human genetic studies have shown that mutations in PLC gamma 2 are associated with autoinflammatory disorders and Alzheimer's disease, and serve as a principal source of diacylglycerol (DAG) in innate immune cells. These DAG pools are converted into bioactive endocannabinoids and eicosanoids by DAG lipase and monoacylglycerol lipase enzymes. Disruption of PLC gamma 2 in mouse microglia results in impaired endocannabinoid-eicosanoid cross-talk and alterations in immune-relevant lipid pathways.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Biographical-Item
Biochemistry & Molecular Biology
Edward A. Dennis, Valerie B. O'Donnell
JOURNAL OF LIPID RESEARCH
(2020)
Article
Biochemistry & Molecular Biology
Daiki Hayashi, Varnavas D. Mouchlis, Edward A. Dennis
Summary: This study reveals the unique substrate selectivity of human phospholipase A2s (PLA2) for different fatty acids, discussing the substrate preferences and active site properties of cytosolic cPLA2 enzymes, calcium-independent iPLA2 enzymes, and secreted sPLA2 enzymes.
JOURNAL OF LIPID RESEARCH
(2021)
Letter
Multidisciplinary Sciences
Harald C. Koefeler, Thomas O. Eichmann, Robert Ahrends, John A. Bowden, Niklas Danne-Rasche, Edward A. Dennis, Maria Fedorova, William J. Griffiths, Xianlin Han, Juergen Hartler, Michal Holcapek, Robert Jirasko, Jeremy P. Koelmel, Christer S. Ejsing, Gerhard Liebisch, Zhixu Ni, Valerie B. O'Donnell, Oswald Quehenberger, Dominik Schwudke, Andrej Shevchenko, Michael J. O. Wakelam, Markus R. Wenk, Denise Wolrab, Kim Ekroos
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Daiki Hayashi, Varnavas D. Mouchlis, Edward A. Dennis
Summary: Glycerophospholipids are major components of cell membranes with diverse fatty acyl chain compositions and polar head groups. Phospholipase A(2) enzymes play a critical role in metabolism by hydrolyzing glycerophospholipids, and different human PLA(2) enzymes show distinct preferences for sn-1 acyl chain linkages.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
(2022)
Article
Multidisciplinary Sciences
Varnavas D. Mouchlis, Daiki Hayashi, Alexis M. Vasquez, Jian Cao, J. Andrew McCammon, Edward A. Dennis
Summary: Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) associates with lipoproteins in human plasma and hydrolyzes oxidized phospholipids. The mechanism of enzyme-membrane association and substrate specificity were studied using lipidomics and mass spectrometry techniques.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Maria A. Theodoropoulou, Anastasia Psarra, Martin Erhardt, Aikaterini Nikolaou, Anna-Dimitra D. Gerogiannopoulou, Dimitra Hadjipavlou-Litina, Daiki Hayashi, Edward A. Dennis, Andrea Huwiler, George Kokotos
Summary: The search for new drugs that can regulate the production of prostaglandin E-2 (PGE(2)) is crucial in the treatment of inflammatory diseases. In this study, we synthesized and evaluated a series of compounds, and identified N-acylated and N-alkylated 2-aminobenzothiazoles as potential leads. These compounds showed significant inhibition of PGE(2) generation in rat mesangial cells and demonstrated better anti-inflammatory activity than indomethacin. The findings suggest that N-acylated or N-alkylated 2-aminobenzothiazoles could be promising candidates for regulating PGE(2) formation.
Article
Multidisciplinary Sciences
Loren M. DeVito, Edward A. Dennis, Barbara B. Kahn, Gerald Shulman, Joseph L. Witztum, Sudeshna Sadhu, Joseph Nickels, Matthew Spite, Susan Smyth, Sarah Spiegel
Summary: Recent research has revealed the cellular and molecular functions of bioactive lipids as signaling molecules in regulating inflammation and lipid metabolism, which can help identify mechanisms targeted to prevent or treat cardiometabolic conditions.
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Edward A. Dennis
Summary: Lipids play important roles in chronic diseases, but defining the substrate specificity of lipid metabolism enzymes is challenging. This research focuses on how membranes interact with enzymes to regulate cell signaling and metabolic pathways. By using substrate lipidomics and molecular dynamics simulations, the study reveals the link between enzyme specificity and hydrophobic binding subsites for membrane phospholipid substrates.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Daiki Hayashi, Varnavas D. Mouchlis, Seika Okamoto, Tomoka Namba, Liuqing Wang, Sheng Li, Shuji Ueda, Minoru Yamanoue, Hirofumi Tachibana, Hiroyuki Arai, Hitoshi Ashida, Edward A. Dennis, Yasuhito Shirai
Summary: Alpha-tocopherol (alpha Toc), the active form of vitamin E, has both antioxidant and non-antioxidant effects. It has been discovered that the membrane-bound 67 kDa laminin receptor (67LR) serves as a receptor for alpha Toc, mediating the non-antioxidant effects such as DGK alpha activation. This study provides the first evidence of a membrane receptor for alpha Toc and one of the underlying mechanisms of its non-antioxidant function.
JOURNAL OF NUTRITIONAL BIOCHEMISTRY
(2022)
Editorial Material
Biochemistry & Molecular Biology
Edward A. Dennis
Summary: The translation describes the author's laboratory research on lipids, focusing on phospholipases and lipidomics, and the evolution of the lipid field. The author also discusses the parallel side stories and activities that influenced their laboratory research and contributed to the development of the LIPID MAPS initiative.
Review
Chemistry, Multidisciplinary
Varnavas D. Mouchlis, Edward A. Dennis
Summary: Water-soluble proteins and membrane-bound proteins interact with membrane surfaces and bind specific lipid molecules. Phospholipases are important enzymes in biological membranes that catalyze hydrolysis reactions by interacting with membranes and extracting phospholipid substrates. The association of phospholipases with membranes induces conformational changes and stabilizes the enzymes in an active state.
ACCOUNTS OF CHEMICAL RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Matthew J. Conroy, Robert M. Andrews, Simon Andrews, Lauren Cockayne, Edward A. Dennis, Eoin Fahy, Caroline Gaud, William J. Griffiths, Geoff Jukes, Maksim Kolchin, Karla Mendivelso, Andrea F. Lopez-Clavijo, Caroline Ready, Shankar Subramaniam, Valerie B. O'Donnell
Summary: LIPID MAPS is a systematic and standardized approach for organizing lipid structural and biochemical data, and it has become the accepted community standard. It provides databases, software tools, and educational resources. The recent expansion of LIPID MAPS includes richer metadata, improved interoperability, and programmatic access. In addition, LIPID MAPS collaborates with WikiPathways to curate pathway data and annotate lipids.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Pathology
Christina M. Mckenzie, Matt Marinkovich, Anibal G. Armien, Judy St. Leger, Aaron M. Armando, Edward A. Dennis, Oswald Quehenberger, Alison Righton
Summary: This study presents the pedigree analysis, clinical manifestations, gross, microscopic, ultrastructural, and lipidomic findings of four female superb bird-of-paradise (SBOP) siblings, revealing a primary inherited glycerolipid storage disease. These birds, offspring of closely related parents, displayed characteristic lesions including tissue distortion due to the accumulation of lipid vacuoles in various organs. Lipidomic profiling confirmed the presence of triacylglycerols in the cytoplasmic lipid deposits. Further investigations, such as genome sequencing and genotyping, are necessary to determine the underlying genetic mechanism of this disease.
VETERINARY PATHOLOGY
(2023)
Review
Chemistry, Multidisciplinary
Varnavas D. Mouchlis, Edward A. Dennis
Summary: Water-soluble proteins and membrane-bound proteins bind specific lipid molecules on membrane surfaces. Phospholipases, especially PLA2, play an important role in hydrolyzing phospholipids. The interaction between PLA2 and membranes can induce conformational changes in PLA2 and activate it for catalysis. These studies provide insights into membrane-protein interactions and related biological functions.
ACCOUNTS OF CHEMICAL RESEARCH
(2022)
Meeting Abstract
Biochemistry & Molecular Biology
E. A. Dennis