Secreted phospholipases A (sPLAs) participate in a very broad spectrum of biological processes through their enzymatic activity and as ligands for membrane and soluble receptors. The physiological roles of sPLAs as enzymes have been very well described, while their functions as ligands are still poorly known. Since the last overview of sPLA-binding proteins (sPLA-BPs) 10 years ago, several important discoveries have occurred in this area. New and more sensitive analytical tools have enabled the discovery of additional sPLA-BPs, which are presented and critically discussed here. The structural diversity of sPLA-BPs reveals sPLAs as very promiscuous proteins, and we offer some structural explanations for this nature that makes these proteins evolutionarily highly advantageous. Three areas of physiological engagement of sPLA-BPs have appeared most clearly: cellular transport and signalling, and regulation of the enzymatic activity of sPLAs. Due to the multifunctionality of sPLAs, they appear to be exceptional pharmacological targets. We reveal the potential to exploit interactions of sPLAs with other proteins in medical terms, for the development of original diagnostic and therapeutic procedures. We conclude this survey by suggesting the priority questions that need to be answered.
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http://dx.doi.org/10.7150/ijbs.68093 | DOI Listing |
Cell Mol Biol Lett
January 2025
Department of Analytical Chemistry, Medical University of Bialystok, Kilinskiego 1, 15-069, Bialystok, Poland.
The skin is a barrier that protects the human body against environmental factors (physical, including solar radiation, chemicals, and pathogens). The integrity and, consequently, the effective metabolic activity of skin cells is ensured by the cell membrane, the important structural and metabolic elements of which are phospholipids. Phospholipids are subject to continuous transformation, including enzymatic hydrolysis (with the participation of phospholipases A, C, and D) to free polyunsaturated fatty acids (PUFAs), which under the influence of cyclooxygenases (COX1/2), lipoxygenases (LOXs), and cytochrome P450 (CYPs P450) are metabolized to various classes of oxylipins, depending on the type of PUFA being metabolized and the enzyme acting.
View Article and Find Full Text PDFRSC Med Chem
January 2025
School of Chemical Sciences, University of Auckland Auckland 1010 New Zealand
Dysregulation of choline phospholipid metabolism and overexpression of phosphatidylcholine-specific phospholipase C (PC-PLC) is implicated in various cancers. Current known enzyme inhibitors include compounds based on a 2-morpholino-5--benzylamino benzoic acid, or hydroxamic acid, scaffold. In this work, 81 compounds were made by modifying this core structure to explore the pharmacophore.
View Article and Find Full Text PDFCell Death Dis
January 2025
Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Pancreatic ductal adenocarcinoma (PDAC) is one of the most malignant tumors because of its high metastatic ability. The glutamine (Gln)-deficient microenvironment contributes to PDAC metastasis; however, the underlying molecular mechanisms remain unclear. Here, we demonstrated that melanophilin (MLPH) promotes PDAC metastasis by inducing the regrowth of primary cilia.
View Article and Find Full Text PDFEcotoxicol Environ Saf
January 2025
Key Laboratory of Environmental Stress and Chronic Disease Control & Prevention (China Medical University), Ministry of Education, Shenyang, Liaoning, China; Department of Occupational and Environmental Health, School of Public Health, China Medical University, Shenyang, Liaoning, China. Electronic address:
Deltamethrin (DM), a broad-spectrum insecticide, is widely used in the world. It can exert direct action on the central nervous system to produce neurotoxicity. Exposure to DM can lead to iron metabolism disorder, oxidative stress and learning and memory dysfunction.
View Article and Find Full Text PDFPlatelets
December 2025
Department of Pharmacology and Physiology, George Washington University, Washington, DC, USA.
Platelet-like particles (PLPs), derived from megakaryocytic cell lines MEG-01 and K-562, are widely used as a surrogate to study platelet formation and function. We demonstrate by RNA-Seq that PLPs are transcriptionally distinct from platelets. Expression of key genes in signaling pathways promoting platelet activation/aggregation, such as the PI3K/AKT, protein kinase A, phospholipase C, and α-adrenergic and GP6 receptor pathways, was missing or under-expressed in PLPs.
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