Article
Oncology
Zhangxiao Peng, Yanxin Chang, Jianhui Fan, Weidan Ji, Changqing Su
Summary: Phospholipase A2 enzymes are a superfamily consisting of six subfamilies, playing important roles in inflammation-related diseases and cancer. Among them, sPLA2-IIA may have conflicting roles depending on cancer type, while cPLA2alpha and iPLA28 generally play a protumorigenic role in most cancers.
Article
Biochemistry & Molecular Biology
Ruhani Sagar, Jinchao Lou, Michael D. Best
Summary: In this work, a bis-pyrene phospholipid probe was designed, synthesized, and applied for the detection of phospholipase A2 (PLA2) activity. The probe exhibited changes in pyrene monomer and excimer fluorescence intensities upon PLA2 action. Continuous fluorometric assays enabled the detection of multiple PLA2 enzymes and the inhibition of PLA2 activity by p-bromo phenacylbromide. Thin-layer chromatography and mass spectrometry analysis confirmed the hydrolysis of the probe by PLA2. The probe also showed cleavage by phospholipase C and D enzymes, although fluorescence changes were not observed. Overall, the developed bis-pyrene phospholipid probe is effective for the detection of PLA2 activity and can be used for inhibitor screening.
BIOORGANIC & MEDICINAL CHEMISTRY
(2023)
Article
Food Science & Technology
Nur Atiqah Haizum Abdullah, Muhamad Rusdi Ahmad Rusmili, Syafiq Asnawi Zainal Abidin, Mohd Farooq Shaikh, Wayne C. Hodgson, Iekhsan Othman
Summary: Phospholipase A(2) (PLA(2)) toxins are a major component of snake venom with various harmful effects. This study isolated a specific PLA(2) toxin from Malaysian Naja sumatrana venom and investigated its activity.
Article
Biochemistry & Molecular Biology
Vania Hinkovska-Galcheva, Taylour Treadwell, Jonathan M. Shillingford, Angela Lee, Akira Abe, John J. G. Tesmer, James A. Shayman
Summary: Phospholipidosis, a pathological response to drugs, is primarily caused by the inhibition of PLA2G15. 36 drugs were found to induce phospholipidosis by inhibiting PLA2G15, with fosinopril being the most potent inhibitor. Inhibiting PLA2G15 provides a potentially robust screening platform for assessing drug toxicity during development.
JOURNAL OF LIPID RESEARCH
(2021)
Article
Cell Biology
Ashish Jaiswal, Rakhshinda Rehman, Joytri Dutta, Sabita Singh, Archita Ray, Malathy Shridhar, Jaswant Jaisankar, Manas Bhatt, Dikshit Khandelwal, Bandya Sahoo, Arjun Ram, Ulaganathan Mabalirajan
Summary: Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease with a poor prognosis. The expression profile of various secretory Phospholipase A2 (PLA2) isoforms in the lungs of healthy individuals and IPF patients was analyzed. PLA2G2A and PLA2G5 were found to be increased in the fibroblasts of IPF patients.
Article
Cell Biology
Kshama Pansare, Bhabani Mohanty, Ranjeeta Dhotre, Aafrin M. Pettiwala, Saili Parab, Neha Gupta, Poonam Gera, Nilesh Gardi, Rucha Dugge, Priyanka Sahu, Ruby Alhans, Pradnya Kowtal, Pradip Chaudhari, Rajiv Sarin
Summary: This study reveals that aspirin inhibits PLA2G6 to exert anti-tumor effects and demonstrates synthetic lethality in AAM pathway down-regulated GB-SCC.
Article
Urology & Nephrology
Nicola M. Tomas, Silke Dehde, Catherine Meyer-Schwesinger, Ming Huang, Irm Hermans-Borgmeyer, Johanna Maybaum, Renke Lucas, Jennie L. von der Heide, Oliver Kretz, Sarah M. S. Koellner, Larissa Seifert, Tobias B. Huber, Gunther Zahner
Summary: This study successfully generated a transgenic mouse line expressing full-length human PLA2R1 in podocytes, which developed membranous nephropathy with characteristics similar to human disease. The mouse model provides a useful tool for evaluating antigen-specific treatment strategies and advancing our understanding of the autoimmune pathogenesis of membranous nephropathy.
KIDNEY INTERNATIONAL
(2022)
Article
Multidisciplinary Sciences
Eric M. Lynch, Michael A. DiMattia, Steven Albanese, Gydo C. P. van Zundert, Jesse M. Hansen, Joel D. Quispe, Madison A. Kennedy, Andreas Verras, Kenneth Borrelli, Angela Toms, Neelu Kaila, Kevin D. Kreutter, Joshua J. McElwee, Justin M. Kollman
Summary: CTPS1 is essential for an effective immune response, with deficiency leading to severe immunodeficiency. CTPS1 expression is up-regulated in activated lymphocytes to meet the increased demand for nucleic acid and lipid synthesis. Selective inhibition of CTPS1 could be beneficial for treating immune disorders and lymphocyte cancers, with recent small-molecule inhibitors showing promise in inhibiting proliferation of human T cells.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Md. Afroz Bakht, Thangaiyan Pooventhiran, Renjith Thomas, Mehnaz Kamal, Israf Ud Din, Najeeb Ur Rehman, Imtiaz Ali, Noushin Ajmal, Mohamed Jawed Ahsan
Summary: Phospholipase A2 (PLA2) promotes inflammation by releasing arachidonic acid (AA), and its elevated level is associated with various diseases. Inhibiting PLA2 can be a potential strategy for treating inflammation by blocking the AA cascade. An efficient method for synthesizing octahydroquinazolinone compounds has been developed, and two compounds show strong inhibitory effects against PLA2 and protease.
Article
Chemistry, Medicinal
Tuan Xu, Md Kabir, Srilatha Sakamuru, Pranav Shah, Elias C. Padilha, Deborah K. Ngan, Menghang Xia, Xin Xu, Anton Simeonov, Ruili Huang
Summary: This study developed predictive models for inhibitors and substrates of CYP3A7/CYP3A4 using chemical structure analysis. The models' performance was evaluated using AUC-ROC, balanced accuracy, and Matthews correlation coefficient. The top performing models can be used to assess the safety and efficacy of new drugs separately for fetuses/neonates and adults, as well as guide the design and optimization of therapeutic drugs.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Chemistry, Organic
Dipanjan Bhattacharyya, Bikash Kumar Sarmah, Sekhar Nandi, Hemant Kumar Srivastava, Animesh Das
Summary: A phosphine-free pincer ruthenium(III) catalyzed beta-alkylation of secondary alcohols with primary alcohols to alpha-alkylated ketones and beta-branched ketones from two different secondary alcohols is reported. This environmentally friendly and atom efficient transformation produces only H2O and H-2 gas as byproducts. The protocol has been successfully scaled up to gram-scale reactions and applied to the functionalization of complex vitamin E and cholesterol derivatives.
Article
Oncology
Jingjin Li, Xiaoping Zhang, Mengxi Yang, Hang Yang, Ning Xu, Xueqiang Fan, Gang Liu, Xintong Jiang, Jiasai Fan, Lifang Zhang, Hu Zhang, Ying Zhou, Rui Li, Si Gao, Jiangli Jin, Zening Jin, Jingang Zheng, Qiang Tu, Jingyi Ren
Summary: Through genome-wide analysis of DNA methylation, it was found that hypomethylation in vulnerable atherosclerotic plaques is associated with genes involved in inflammation, indicating a potential role in driving the progression and destabilization of atherosclerotic cardiovascular disease.
CLINICAL EPIGENETICS
(2021)
Article
Biochemistry & Molecular Biology
Luke A. Spear, Yang Huang, Jinghao Chen, Alexander R. Nodling, Satpal Virdee, Yu-Hsuan Tsai
Summary: A general approach for rapid and selective inhibition of enzymes in cells using a common tool compound is proposed. This chemogenetic strategy allows for bioorthogonal tethering of inhibitors to target enzymes. The scope of this approach is expanded to cysteine-dependent enzymes, enabling selective inhibition in biochemical assays.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Liangbo Hu, Ying Li, Xinhui Lin, Yucheng Huo, Hongyue Zhang, Huaimin Wang
Summary: By designing, synthesizing, and assembling an enzymatic programmable peptide system, we induced molecular assemblies formation spatiotemporally in living cancer cells, resulting in mainly necroptosis of glioblastoma cells. The stability and glycosylation of molecules play a crucial role in determining the bioactivity, as evidenced by detailed mechanistic studies showing site-specific formation of assemblies capable of activating the downstream cell death pathway.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Urology & Nephrology
Sheng Hu, Ru Huang, Patrick Keller, Melanie Goetz, Alexander Tamalunas, Philipp Weinhold, Raphaela Waidelich, Christian G. G. Stief, Martin Hennenberg
Summary: This study found that phospholipase A(2) (PLA(2)) plays a role in the contraction of prostate smooth muscle, but α(1)-adrenergic contraction is independent of PLA(2). These findings are important for understanding the mechanism of prostate muscle contraction and the treatment of voiding symptoms caused by benign prostatic hyperplasia.
NEUROUROLOGY AND URODYNAMICS
(2023)
Article
Gastroenterology & Hepatology
Hsiao-Yen Ma, Gen Yamamoto, Jun Xu, Xiao Liu, Daniel Karin, Ju Youn Kim, Ludmil B. Alexandrov, Yukinori Koyama, Takahiro Nishio, Chris Benner, Sven Heinz, Sara B. Rosenthal, Shuang Liang, Mengxi Sun, Gabriel Karin, Peng Zhao, Pnina Brodt, Lain H. Mckillop, Oswald Quehenberger, Ed Dennis, Alan Saltiel, Hidekazu Tsukamoto, Bin Gao, Michael Karin, David A. Brenner, Tatiana Kisseleva
JOURNAL OF HEPATOLOGY
(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