Review
Biochemistry & Molecular Biology
Beatriz A. Rodas-Junco, Graciela E. Racagni-Di-Palma, Michel Canul-Chan, Javier Usorach, S. M. Teresa Hernandez-Sotomayor
Summary: Plants have developed mechanisms to process extracellular signals through transient molecules known as second messengers, which can modulate physiological responses and gene expression under stress conditions. Recent research has focused on the molecular mechanisms of lipid second messengers in response to osmotic stress, highlighting their ability to recruit target proteins to the membrane and affect protein function.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Ana Gomez-Larrauri, Patricia Gangoiti, Natalia Presa, Asier Dominguez-Herrera, Chiara Donati, Paola Bruni, Miguel Trueba, Antonio Gomez-Munoz, Alberto Ouro
Summary: Phosphatidic acid stimulates myoblast proliferation through interaction with LPA1 and LPA2 receptors, activating the PI3K/Akt and MEK/ERK1-2 pathways.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Pathology
Kuniyuki Kano, Junken Aoki, Timothy Hla
Summary: Lysophospholipids, such as lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P), are important extracellular lipid mediators that signal through specific G protein-coupled receptors. They play crucial roles in various biological processes and diseases, including cellular stress signaling, inflammation, and host defense responses. LPA is involved in regulating fibrosis, neuropathic pain, abnormal angiogenesis, endometriosis, and neuroectodermal developmental disorders, while S1P controls collective behavior, apoptotic cell clearance, and immunesurveillance of cancers. The study of lysophospholipids has led to the development of new therapeutics for autoimmune diseases and holds promise for future treatments of fibrotic disorders, vascular diseases, and cancer.
ANNUAL REVIEW OF PATHOLOGY-MECHANISMS OF DISEASE
(2022)
Review
Pharmacology & Pharmacy
Shun Yaginuma, Jumpei Omi, Kuniyuki Kano, Junken Aoki
Summary: Accumulating evidence suggests that lysophospholipids (LPL) serve as lipid mediators that exert their diverse pathophysiological functions via G protein-coupled receptors. These LPLs can be detected and quantified in various biological fluids and are potential biomarkers for pathological conditions. This review discusses the potential of LPLs and their synthetic enzymes as pathological biomarkers, including methods and problems in their measurement.
PHARMACOLOGY & THERAPEUTICS
(2023)
Article
Biochemistry & Molecular Biology
Yani Arhab, Karim Bessaa, Houda Abla, Meryem Aydin, Renaud Rahier, Arnaud Comte, Leyre Brizuela, Saida Mebarek, Florent Perret, Mickael Cherrier, Abdelkarim Abousalham, Alexandre Noiriel
Summary: This study investigates the impact of structural modifications of PLD inhibitors on enzyme activity and aims to identify new potent inhibitors of eukaryotic PLDs. Vanadate was found to be the most potent inhibitor among all, with an IC50 of around 58 μM. Screening a chemical library of 3120 compounds helped optimize the screening process and paved the way for the discovery of new potent inhibitors.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Article
Chemistry, Multidisciplinary
Veronica Egas Ortuno, Sunil Pulletikurti, Kollery S. Veena, Ramanarayanan Krishnamurthy
Summary: This study presents a robust synthesis method for cyclic phosphatidic acids (cPAs) and investigates their hydrolytic properties, which could advance the understanding of their biological properties and potential use as components of synthetic cells.
CHEMICAL COMMUNICATIONS
(2022)
Article
Plant Sciences
Valerie Wattelet-Boyer, Marina Le Guedard, Franziska Dittrich-Domergue, Lilly Maneta-Peyret, Verena Kriechbaumer, Yohann Boutte, Jean-Jacques Bessoule, Patrick Moreau
Summary: Phosphatidic acid and lysophosphatidic acid acyltransferases play a critical role in the efficiency of intracellular protein trafficking in Arabidopsis thaliana root cells.
JOURNAL OF EXPERIMENTAL BOTANY
(2022)
Article
Biochemistry & Molecular Biology
Yang Zhao, Stephan Hasse, Myriam Vaillancourt, Chenqi Zhao, Lynn Davis, Eric Boilard, Paul Fortin, John Di Battista, Patrice E. Poubelle, Sylvain G. Bourgoin
Summary: PLA1A may play a crucial role in rheumatic diseases, as indicated by elevated levels of PLA1A in the plasma of EA and SLE patients, and high concentrations in the synovial fluids of rheumatoid arthritis patients. The data suggests that PLA1A mediates pro-inflammatory responses through the ATX-LPA receptor signaling axis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Medicine, Research & Experimental
Colin Niaudet, Bongnam Jung, Andrew Kuo, Steven Swendeman, Edward Bull, Takahiro Seno, Reed Crocker, Zhongjie Fu, Lois E. H. Smith, Timothy Hla
Summary: This study reveals the significance of S1P in vascular development. Activation of endothelial S1PR1 by circulating HDL-S1P can suppress neovascularization in retinopathy. These findings suggest that circulating HDL-S1P activation of endothelial S1PR1 serves as a protective mechanism against neovascular retinopathy.
EMBO MOLECULAR MEDICINE
(2023)
Review
Medicine, General & Internal
Yumi Tsuchida, Hirofumi Shoda, Tetsuji Sawada, Keishi Fujio
Summary: Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease characterized by the production of autoantibodies and immune complex deposition. Autotaxin (ATX), which catalyzes the production of lysophosphatidic acid, has been identified as a potential biomarker in SLE. Increased levels of ATX have been found in the serum and urine of patients with SLE and lupus nephritis. Recent studies suggest that ATX produced by plasmacytoid dendritic cells may have an important role in SLE pathogenesis, and it is associated with type I interferons. ATX may be a valuable biomarker and key molecule in SLE.
FRONTIERS IN MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Huasheng Cao, Rong Gong, Shu Yuan, Yuan Su, Weixin Lv, Yimeng Zhou, Qingqing Zhang, Xianjun Deng, Pan Tong, Shihu Liang, Xuemin Wang, Yueyun Hong
Summary: Phospholipase D (PLD) and phosphatidic acid (PA) positively mediate gibberellin (GA) signaling in rice by binding to the soluble GA receptor GID1, regulating the plant's sensitivity to GA, affecting GID1's nuclear localization, and influencing the degradation of DELLA proteins.
Article
Chemistry, Multidisciplinary
Reika Tei, Saket R. Bagde, J. Christopher Fromme, Jeremy M. Baskin
Summary: Cellular membranes contain a wide variety of lipids, but understanding the functions of individual lipids is challenging due to a lack of methods to control membrane composition. In this study, the researchers developed a strategy for editing phospholipids using a bacterial enzyme called phospholipase D. They used directed enzyme evolution in mammalian cells to enhance the activity of the enzyme and demonstrated its utility for editing phospholipids in live cells and synthesizing designer phospholipids in vitro. This approach can be generalized to engineer other chemoenzymatic biomolecule editors.
Article
Biochemistry & Molecular Biology
Aamir Ali Shaikh, Alfatih Alamin, Chenxi Jia, Wei Gong, Xianjun Deng, Qingwen Shen, Yueyun Hong
Summary: Phosphatidic acid (PA) is a key signal molecule involved in osmotic stress responses in plants. LPAT2-derived PA plays a crucial role in salt and drought stress tolerance in rice by mediating ABA response and regulating ion homeostasis and protein kinase signaling pathways.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Plant Sciences
Sang-Chul Kim, Shuaibing Yao, Qun Zhang, Xuemin Wang
Summary: This study reveals the cellular and molecular mechanism of heat-induced nuclear translocation of cytosolic GAPC in Arabidopsis thaliana. PLD delta and PA play critical roles in this process, mediated by lipid-protein interaction. These findings suggest a cellular conduit linking stress perturbations at cell membranes to nuclear functions in plants coping with heat stress.
Article
Biochemistry & Molecular Biology
Yeun Ju Kim, Nivedita Sengupta, Mira Sohn, Amrita Mandal, Joshua G. Pemberton, Uimook Choi, Tamas Balla
Summary: This study reveals that the metabolic fate of newly synthesized phosphatidic acid (PA), the lipid precursor of phosphatidylinositol (PI), is influenced by the fatty acyl-CoA used, leading to preferential routing of the arachidonoyl-enriched species towards PI synthesis. Additionally, the unsaturated forms of PI(4,5P)(2) are replenished faster than the saturated forms during PLC activation, indicating a favored recycling of the unsaturated forms of the PLC-generated hydrolytic products. CDS2 contributes to increased PI resynthesis during PLC activation, while Nir2 contributes to rapid PPIn resynthesis, but the faster re-synthesis of the 38:4 species does not depend on Nir2. Therefore, the fatty acid side-chain composition of the lipid precursors used for PI synthesis is an important determinant of their metabolic fates and the maintenance of the unique fatty acid profile of PPIn lipids.
Review
Endocrinology & Metabolism
Renu A. Kowluru, Ghulam Mohammad
Summary: Diabetes is a life-long disease that damages the body's microvasculature and macrovasculature, affecting metabolic and molecular pathways. External factors such as environmental factors, lifestyle, and pollutants can also regulate gene expression and contribute to disease development. Epigenetic modifications play a crucial role in the development of diabetes and its complications.
METABOLISM-CLINICAL AND EXPERIMENTAL
(2022)
Article
Biochemistry & Molecular Biology
Graciela Andrei, Pierre Fiten, Marcela Krecmerova, Ghislain Opdenakker, Dimitrios Topalis, Robert Snoeck
Summary: Despite the eradication of smallpox, poxviruses still pose a threat to humans and animals. This study characterizes the phenotypic and genotypic features of drug-resistant poxvirus DNA polymerase mutants and identifies amino acid changes associated with drug resistance. The study also highlights the importance of specific residues and identifies several novel mutations associated with different drug-susceptibility patterns.
Article
Ophthalmology
Ahmed M. Abu El-Asrar, Faisal A. Al Rashed, Abdulrahman F. AlBloushi, Mohannad F. Tobaigy, Priscilla W. Gikandi, Carl P. Herbort, Ghislain Opdenakker
Summary: This study found that the timing of treatment initiation is related to disease outcomes in initial-onset acute uveitis associated with Vogt-Koyanagi-Harada disease. It suggests that there is a therapeutic window of opportunity before the appearance of anterior segment inflammation, and initiating effective treatment during this phase can cure uveitis and prevent blinding complications.
ACTA OPHTHALMOLOGICA
(2023)
Article
Biochemistry & Molecular Biology
Ahmed M. Abu El-Asrar, Mohd Imtiaz Nawaz, Eef Allegaert, Mohammad Mairaj Siddiquei, Ajmal Ahmad, Priscilla Gikandi, Gert De Hertogh, Ghislain Opdenakker
Summary: We studied the expression of ADAMTS proteinases and MMP-15 in the ocular microenvironment of PDR patients. We found that ADAMTS proteinases and MMP-15 levels were increased in the vitreous of PDR patients, and the cleavage products of versican and biglycan were also increased. ADAMTS proteinases were localized in endothelial cells, monocytes/macrophages, and myofibroblasts in PDR membranes, with ADAMTS-4 being expressed in the highest number of stromal cells. The angiogenic activity of PDR membranes correlated significantly with the expression of ADAMTS-1 and -4.
Review
Immunology
Ghislain Opdenakker, Severine Vermeire, Ahmed Abu El-Asrar
Summary: Crohn's disease and ulcerative colitis are inflammatory bowel diseases involving immune cells and molecules, with challenges in understanding the mechanisms of therapies, including the role of MMPs.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Rafaela Vaz Sousa Pereira, Estefania Ugarte-Berzal, Jennifer Vandooren, Karin Nylander, Erik Martens, Lieve Van Mellaert, Jo Van Damme, Jan Jeroen Vranckx, Patrick Matthys, Tiina Alamae, Mia Phillipson, Triinu Visnapuu, Ghislain Opdenakker
Summary: This study confirmed the in vitro antibacterial effects of the amylose derivative chlorite-oxidized oxyamylose (COAM) against opportunistic bacterial pathogens common to skin wounds. It also demonstrated that COAM modulates macrophage contents in mouse skin wounds.
JOURNAL OF INFLAMMATION RESEARCH
(2022)
Article
Endocrinology & Metabolism
Jay Kumar, Ghulam Mohammad, Kumari Alka, Renu A. Kowluru
Summary: Mitochondrial dysfunction plays a critical role in the development of diabetic retinopathy. Hyperglycemia downregulates the mtDNA-encoded LncRNA cytochrome B (LncCytB) in retinal endothelial cells, leading to impaired mtDNA packaging and increased vulnerability to damage.
Review
Chemistry, Medicinal
Mieke Metzemaekers, Bert Malengier-Devlies, Mieke Gouwy, Lien De Somer, Fernando de Queiroz Cunha, Ghislain Opdenakker, Paul Proost
Summary: Neutrophils are powerful effector cells that play crucial roles in fighting pathogens and modulating immune responses. Recent evidence suggests that these cells are more versatile and heterogeneous than previously thought, and are involved in various diseases including cancer and autoimmune disorders. This review discusses the kinetics of neutrophils and their activation products, as well as their multifaceted functions in health and disease, focusing on studies using primary human cells.
MEDICINAL RESEARCH REVIEWS
(2023)
Review
Rheumatology
Bernard Grillet, Rafaela Vaz Sousa Pereira, Jo Van Damme, Ahmed Abu El-Asrar, Paul Proost, Ghislain Opdenakker
Summary: Proteolysis of the extracellular matrix is an irreversible post-translational modification in arthropathies like osteoarthritis and rheumatoid arthritis due to increased levels of matrix remodelling enzymes such as matrix metalloproteinases (MMPs). MMPs destroy proteoglycans, collagens, and other ECM molecules and also control joint remodelling indirectly through cell-surface receptors and cytokines. Understanding the regulation and activities of MMPs can help develop better diagnostics and therapies for joint diseases. MMPs play a significant role in irreversible joint remodelling in rheumatoid arthritis and osteoarthritis, making them important targets for precision medicine and diagnosis.
NATURE REVIEWS RHEUMATOLOGY
(2023)
Article
Immunology
Rafaela Vaz Sousa Pereira, Mostafa EzEldeen, Estefania Ugarte-Berzal, Erik Martens, Bert Malengier-Devlies, Jennifer Vandooren, Jan Jeroen Vranckx, Patrick Matthys, Ghislain Opdenakker
Summary: This study found that using physiological fibrin hydrogels in skin wound healing in mice can modulate immune cells and molecules, leading to faster wound repair. The hydrogels can reduce neutrophil numbers, increase non-classical Ly6Clow monocytes and resolutive macrophage populations, and decrease the expression of pro-inflammatory cytokines. Additionally, the hydrogels can increase the counts of dermal endothelial cells, fibroblasts, and keratinocytes, promote keratinocyte migration, and accelerate wound healing.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Ahmed M. Abu El-Asrar, Gert De Hertogh, Eef Allegaert, Mohd I. Nawaz, Sara Abouelasrar Salama, Priscilla W. Gikandi, Ghislain Opdenakker, Sofie Struyf
Summary: Inflammation and fibrosis are key features of proliferative vitreoretinal disorders. The process of macrophage-myofibroblast transition (MMT) may contribute to myofibroblast formation in epiretinal membranes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Jo Van Damme, Ghislain Opdenakker, Sam Van Damme, Sofie Struyf
Summary: Polyclonal antisera from patients have been vital in understanding autoimmune diseases, while monoclonal antibodies are now widely used in cancer and inflammatory disease treatment. The combination of antisera and antibodies with traditional testing methods has played a crucial role in the discovery of new cytokines such as interleukin-1, -6 and -8. However, immunological detection/quantification systems using polyclonal or monoclonal antibodies can be prone to misinterpretation due to posttranslational modifications of analytes.
EUROPEAN CYTOKINE NETWORK
(2023)
Article
Biochemistry & Molecular Biology
Ahmed M. Abu El-Asrar, Mohd I. Nawaz, Ajmal Ahmad, Luna Dillemans, Mairaj Siddiquei, Eef Allegaert, Priscilla W. Gikandi, Gert De Hertogh, Ghislain Opdenakker, Sofie Struyf
Summary: This study aimed to investigate the role of the CD40-CD40 ligand (CD40L) pathway in inflammation-mediated angiogenesis in proliferative diabetic retinopathy (PDR). The results showed that CD40L and CD40 levels were significantly increased in PDR vitreous samples. CD40L and CD40 expression were observed in vascular endothelial cells, leukocytes, and myofibroblasts in epiretinal membranes. Moreover, the researchers found that sCD40L increased retinal vascular permeability and upregulated the expression of VEGF, ICAM-1, and VCAM-1. The study also demonstrated that TNF-alpha and VEGF could regulate the expression of CD40 in HRMECs and Muller cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
