The effect of two structurally distinct tyrosine kinase inhibitors, genistein (100 microM) and methyl-2, 5-dihydroxycinnamate (25 microM) on ATP- and thapsigargin-induced Ca2+ signals in Fura-2-loaded rat peritoneal macrophages was investigated. Both compounds were shown to inhibit ATP-evoked Ca2+ entry but not to release from internal stores. Both compounds also inhibit the store-dependent or "capacitative" Ca2+ influx stimulated by emptying the intracellular Ca2+ stores with endoplasmic Ca(2+)-ATPase inhibitor thapsigargin (100 nM). Genistein and methyl-2, 5-dihydroxycinnamate have no effect on Ca2+ release from intracellular stores. Tyrosine phosphatase inhibitor orthovanadate Na (50 microM) increases ATP-induced Ca2+ entry but does not prevent the inhibitory effect of genistein. These data are compatible with the role played by tyrosine phosphorylation in the control of Ca2+ entry in rat peritoneal macrophages.
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BMC Med
January 2025
Physiological Institute, University of Regensburg, University Street 31, 93053, Regensburg, Germany.
Background: Dystonia is a common neurological hyperkinetic movement disorder that can be caused by mutations in anoctamin 3 (ANO3, TMEM16C), a phospholipid scramblase and ion channel. We previously reported patients that were heterozygous for the ANO3 variants S651N, V561L, A599D and S651N, which cause dystonia by unknown mechanisms.
Methods: We applied electrophysiology, Ca measurements and cell biological methods to analyze the molecular mechanisms that lead to aberrant intracellular Ca signals and defective activation of K channels in patients heterozygous for the ANO3 variants.
Cells
December 2024
Department of Physiology, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea.
Injured or atrophied adult skeletal muscles are regenerated through terminal differentiation of satellite cells to form multinucleated muscle fibers. Transplantation of satellite cells or cultured myoblasts has been used to improve skeletal muscle regeneration. Some of the limitations observed result from the limited number of available satellite cells that can be harvested and the efficiency of fusion of cultured myoblasts with mature muscle fibers (i.
View Article and Find Full Text PDFAm J Physiol Cell Physiol
January 2025
Department of Physiology (Cellular Physiology Research Group),Institute of Molecular Pathology Biomarkers (IMPB), University of Extremadura, 10003-Caceres, Spain.
Filamin A (FLNA) is an actin-binding protein that has been reported to interact with STIM1 modulating the activation of Orai1 channels. Cleaving of FLNA by calpain leads to a C-terminal fragment that is involved in a variety of functional and pathological events, including pro-oncogenic activity in different types of cancer. Here we show that full-length FLNA is downregulated in samples from colon cancer patients as well as in the adenocarcinoma cell line HT-29.
View Article and Find Full Text PDFJ Biol Chem
December 2024
Department of Pharmacology, Addiction Science, and Toxicology, College of Medicine, The University of Tennessee Health Science Center; Memphis, 38163. Electronic address:
Familial Alzheimer's disease (FAD) is frequently associated with mutations in the amyloid precursor protein (APP), which are thought to lead to cognitive deficits by impairing NMDA receptor (NMDAR)-dependent forms of synaptic plasticity. Given the reliance of synaptic plasticity on NMDAR-mediated Ca entry, shaping of NMDAR activity by APP and/or its disease-causing variants could provide a basis for understanding synaptic plasticity impairments associated with FAD. A region of APP (residues 639-644 within APP695) processed by the γ-secretase complex, which generates amyloid β (Aβ) peptides, is a hotspot for FAD mutations.
View Article and Find Full Text PDFToxins (Basel)
December 2024
Univ. Angers, INSERM, CNRS, MITOVASC, Equipe CarME, SFR ICAT, 49000 Angers, France.
The vegetal alkaloid toxin veratridine (VTD) is a selective voltage-gated Na (Na) channel activator, widely used as a pharmacological tool in vascular physiology. We have previously shown that Na channels, expressed in arteries, contribute to vascular tone in mouse mesenteric arteries (MAs). Here, we aimed to better characterize the mechanisms of action of VTD using mouse cecocolic arteries (CAs), a model of resistance artery.
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