It was discovered that there is sphingomyelinase activity in the rat liver nuclei. The maximum of enzyme activity is at pH 7.1. The data obtained demonstrated that the main part of sphingomyelinase is located in the nuclear membrane. Comparison of sphingomyelinase activity in cell nuclei, liver and brain homogenates shows high level of enzyme activity in the nuclei. The authors discuss possible participation of sphingomyelinases in changes of phospholipids composition in nuclear structure under different functional activity of cell nuclei.
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Virology
December 2024
Departments of Surgery & Molecular Microbiology and Immunology, University of Missouri, Columbia, MO, 65212, USA. Electronic address:
The sphingolipid network is sustained principally by the balance of bioactive sphingolipid molecules and their regulation by sphingolipid-metabolizing enzymes. The components in the lipid system display key functions in numerous cellular and disease conditions including virus infections. During the COVID-19 pandemic, there was a fruitful effort to use an inhibitor that blocks the activity of sphingosine kinase (SphK) 2 to cure the devastating disease.
View Article and Find Full Text PDFFront Immunol
January 2025
Department of Biophysics and Cell Biology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
The human voltage-gated proton channel (H1) provides an efficient proton extrusion pathway from the cytoplasm contributing to the intracellular pH regulation and the oxidative burst. Although its pharmacological inhibition was previously shown to induce cell death in various cell types, no such effects have been examined in polarized macrophages albeit H1 was suggested to play important roles in these cells. This study highlights that 5-chloro-2-guanidinobenzimidazole (ClGBI), the most widely applied H1 inhibitor, reduces the viability of human THP-1-derived polarized macrophages at biologically relevant doses with M1 macrophages being the most, and M2 cells the least sensitive to this compound.
View Article and Find Full Text PDFBioorg Chem
December 2024
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Gazi University, 06330 Ankara, Türkiye. Electronic address:
Bacillus cereus sphingomyelinase C (B. cereus SMase), which plays a crucial role in bacterial virulence, has emerged as a new therapeutic target for treating opportunistic infections caused by this pathogen. It also shares catalytic domain similarity with human neutral sphingomyelinase 2 (nSMase2), which is implicated in Alzheimer's disease.
View Article and Find Full Text PDFPLoS One
December 2024
Department of Pharmacy, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.
Drug resistance of cancers remains a major obstacle due to limited therapeutics. Lysosome targeting is an effective method for overcoming drug resistance in cancer cells. St-N (ent-13-hydroxy-15-kaurene-19-acid N-methylpiperazine ethyl ester) is a novel alkaline stevioside derivative with an amine group.
View Article and Find Full Text PDFInt J Neonatal Screen
December 2024
Division of Inherited Metabolic Diseases, Department of Women's and Children's Health, University Hospital of Padua, 35128 Padua, Italy.
Acid sphingomyelinase deficiency (ASMD) is a rare lysosomal storage disorder with a broad clinical spectrum. Early diagnosis and initiation of treatment are crucial for improving outcomes, yet the disease often goes undiagnosed due to its rarity and phenotypic heterogeneity. This study aims to evaluate the feasibility and disease incidence of newborn screening (NBS) for ASMD in Italy.
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