Ca2+ Signaling in Cardiac Fibroblasts: An Emerging Signaling Pathway Driving Fibrotic Remodeling in Cardiac Disorders

Biomedicines, Journal Year: 2025, Volume and Issue: 13(3), P. 734 - 734

Published: March 17, 2025

Cardiac fibrosis is a scarring event that occurs in the myocardium response to multiple cardiovascular disorders, such as acute myocardial infarction (AMI), ischemic cardiomyopathy, dilated hypertensive heart disease, inflammatory diabetic and aortic stenosis. Fibrotic remodeling mainly sustained by differentiation of fibroblasts into myofibroblasts, which synthesize secrete most extracellular matrix (ECM) proteins. An increase intracellular Ca2+ concentration ([Ca2+]i) cardiac emerging critical mediator fibrogenic signaling cascade. Herein, we review mechanisms may shape signals involved fibroblast transdifferentiation myofibroblasts. We focus our attention on functional interplay between inositol-1,4,5-trisphosphate (InsP3) receptors (InsP3Rs) store-operated entry (SOCE). In accordance with this, InsP3Rs SOCE drive elicited Gq-protein coupled (GqPCRs) promote fibrotic remodeling. Then, describe additional sustain entry, including receptor-operated (ROCE), P2X receptors, Transient Receptor Potential (TRP) channels, Piezo1 channels. parallel, discuss pharmacological manipulation handling machinery promising approach mitigate or reverse disorders.

Language: Английский

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Gamma-Aminobutyric Acid Signaling in Damage Response, Metabolism, and Disease

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(5), P. 4584 - 4584

Published: Feb. 26, 2023

Gamma-aminobutyric acid (GABA) plays a crucial role in signal transduction and can function as neurotransmitter. Although many studies have been conducted on GABA brain biology, the cellular physiological relevance of other metabolic organs remain unclear. Here, we will discuss recent advances understanding metabolism with focus its biosynthesis functions organs. The mechanisms liver biology disease revealed new ways to link function. By reviewing what is known about distinct effects GABA-mediated metabolites pathways, provide framework for newly identified targets regulating damage response, implications ameliorating diseases. With this review, suggest that further research necessary develop GABA’s beneficial toxic progression.

Language: Английский

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The Molecular Heterogeneity of Store-Operated Ca2+ Entry in Vascular Endothelial Cells: The Different roles of Orai1 and TRPC1/TRPC4 Channels in the Transition from Ca2+-Selective to Non-Selective Cation Currents

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(4), P. 3259 - 3259

Published: Feb. 7, 2023

Store-operated Ca2+ entry (SOCE) is activated in response to the inositol-1,4,5-trisphosphate (InsP3)-dependent depletion of endoplasmic reticulum (ER) store and represents a ubiquitous mode influx. In vascular endothelial cells, SOCE regulates plethora functions that maintain cardiovascular homeostasis, such as angiogenesis, tone, permeability, platelet aggregation, monocyte adhesion. The molecular mechanisms responsible for activation cells have engendered long-lasting controversy. Traditionally, it has been assumed mediated by two distinct ion channel signalplexes, i.e., STIM1/Orai1 STIM1/Transient Receptor Potential Canonical 1(TRPC1)/TRPC4. However, recent evidence shown Orai1 can assemble with TRPC1 TRPC4 form non-selective cation intermediate electrophysiological features. Herein, we aim at bringing order mediate tree from multiple species (e.g., human, mouse, rat, bovine). We propose three currents cells: (1) Ca2+-selective Ca2+-release current (ICRAC), which STIM1 Orai1; (2) store-operated (ISOC), STIM1, TRPC1, TRPC4; (3) moderately Ca2+-selective, ICRAC-like current, TRPC4, Orai1.

Language: Английский

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The Impact of Fermented Gamma-Aminobutyric Acid on Poultry Growth Performance Through Insulin-like Growth Factor-1 Activation

Fermentation, Journal Year: 2025, Volume and Issue: 11(2), P. 84 - 84

Published: Feb. 7, 2025

Gamma-aminobutyric acid (GABA) is becoming more well-acknowledged for its ability to improve the development performance of poultry, particularly by interacting with Insulin-like growth Factor 1 (IGF-1) pathway. This review emphasizes importance GABA in optimizing poultry production thoroughly examining biochemical characteristics, physiological roles, and molecular mechanisms action. a crucial inhibitory neurotransmitter that not only regulates neuronal excitability but also optimizes metabolic processes critical growth. Supplementing feeds has been shown enhance feed conversion efficiency, increase body weight, bolster immune function. The interplay between IGF-1 crucial, as modulates levels receptor sensitivity, promoting muscle overall health. fermentation producing bioavailable GABA, presenting promising implications sustainable farming practices. Further investigation into supplementation strategies could lead improved healthier systems.

Language: Английский

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Transient Receptor Potential Ankyrin 1 (TRPA1) Channel as a Sensor of Oxidative Stress in Cancer Cells

Cells, Journal Year: 2023, Volume and Issue: 12(9), P. 1261 - 1261

Published: April 26, 2023

Moderate levels of reactive oxygen species (ROS), such as hydrogen peroxide (H2O2), fuel tumor metastasis and invasion in a variety cancer types. Conversely, excessive ROS can impair growth by triggering cell death. In order to cope with the oxidative stress imposed microenvironment, malignant cells exploit sophisticated network antioxidant defense mechanisms. Targeting capacity or enhancing their sensitivity ROS-dependent death represent promising strategy for alternative anticancer treatments. Transient Receptor Potential Ankyrin 1 (TRPA1) is redox-sensitive non-selective cation channel that mediates extracellular Ca2+ entry upon an increase intracellular levels. The ensuing concentration turn engage non-canonical program induce mitochondrial dysfunction apoptotic depending on type. Herein, we sought describe opposing effects TRPA1 activation fate propose pharmacological manipulation therapeutic enhance stress.

Language: Английский

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Cracking the Endothelial Calcium (Ca2+) Code: A Matter of Timing and Spacing

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(23), P. 16765 - 16765

Published: Nov. 26, 2023

A monolayer of endothelial cells lines the innermost surface all blood vessels, thereby coming into close contact with every region body and perceiving signals deriving from both bloodstream parenchymal tissues. An increase in intracellular Ca2+ concentration ([Ca2+]i) is main mechanism whereby vascular integrate information conveyed by local circulating cues. Herein, we describe dynamics spatial distribution to understand how an array spatially restricted (at subcellular cellular levels) exploited intima fulfill this complex task. We then illustrate affect most appropriate function are integrated transmit more distant sites maintain cardiovascular homeostasis. Vasorelaxation sprouting angiogenesis were selected as example functions that finely tuned variable spatio-temporal profile signals. further highlighted distinct signatures regulate different phases vasculogenesis, i.e., proliferation migration, precursors.

Language: Английский

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Intracellular Ca2+ signalling: unexpected new roles for the usual suspect

Frontiers in Physiology, Journal Year: 2023, Volume and Issue: 14

Published: July 27, 2023

Cytosolic Ca 2+ signals are organized in complex spatial and temporal patterns that underlie their unique ability to regulate multiple cellular functions. Changes intracellular concentration ([Ca ] i ) finely tuned by the concerted interaction of membrane receptors ion channels introduce into cytosol, -dependent sensors effectors translate elevation [Ca a biological output, -clearing mechanisms return pre-stimulation levels prevent cytotoxic overload. The assortment handling machinery varies among different cell types generate selectively tailored subserve specific advent novel high-speed, 2D 3D time-lapse imaging techniques, single-wavelength genetic indicators, as well development engineering tools manipulate single cells whole animals, has shed light on regulation activity machinery. A symposium within framework 72nd Annual Meeting Italian Society Physiology, held Bari 14–16th September 2022, recently addressed many unexpected whereby signalling regulates fate healthy disease states. Herein, we present report this symposium, which following emerging topics were discussed: 1) Regulation water reabsorption kidney lysosomal release through Transient Receptor Potential Mucolipin 1 (TRPML1); 2) Endoplasmic reticulum-to-mitochondria transfer Alzheimer’s disease-related astroglial dysfunction; 3) non-canonical role TRP Melastatin 8 (TRPM8) Rap1A inhibitor definition some cancer hallmarks; 4) Non-genetic optical stimulation cardiovascular system.

Language: Английский

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Two Signaling Modes Are Better than One: Flux-Independent Signaling by Ionotropic Glutamate Receptors Is Coming of Age

Biomedicines, Journal Year: 2024, Volume and Issue: 12(4), P. 880 - 880

Published: April 16, 2024

Glutamate is the major excitatory neurotransmitter in central nervous system. Glutamatergic transmission can be mediated by ionotropic glutamate receptors (iGluRs), which mediate rapid synaptic depolarization that associated with Ca2+ entry and activity-dependent change strength of transmission, as well metabotropic (mGluRs), slower postsynaptic responses through recruitment second messenger systems. A wealth evidence reported over last three decades has shown this dogmatic subdivision between iGluRs mGluRs may not reflect actual physiological signaling mode iGluRs, i.e., α-amino-3-hydroxy-5-methyl-4-isoxasolepropionic acid (AMPA) (AMPAR), kainate (KARs), N-methyl-D-aspartate (NMDA) (NMDARs). Herein, we review available supporting notion canonical recruit flux-independent pathways only neurons, but also brain astrocytes cerebrovascular endothelial cells. Understanding versatility exert a profound impact on our understanding glutamatergic synapses. Furthermore, it shed light novel neuroprotective strategies against disorders.

Language: Английский

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The Unexpected Role of the Endothelial Nitric Oxide Synthase at the Neurovascular Unit: Beyond the Regulation of Cerebral Blood Flow

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(16), P. 9071 - 9071

Published: Aug. 21, 2024

Nitric oxide (NO) is a highly versatile gasotransmitter that has first been shown to regulate cardiovascular function and then exert tight control over much broader range of processes, including neurotransmitter release, neuronal excitability, synaptic plasticity. Endothelial NO synthase (eNOS) usually far from the mind neurophysiologists, who have focused most their attention on (nNOS) as primary source at neurovascular unit (NVU). Nevertheless, available evidence suggests eNOS could also contribute generating burst that, serving volume intercellular messenger, produced in response activity brain parenchyma. Herein, we review role both regulation cerebral blood flow plasticity discuss mechanisms by which cerebrovascular endothelial cells may transduce inputs into signal. We further suggest play critical vascular-to-neuronal communication integrating signals converging onto streaming active neurons.

Language: Английский

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Allyl Isothiocianate Induces Ca2+ Signals and Nitric Oxide Release by Inducing Reactive Oxygen Species Production in the Human Cerebrovascular Endothelial Cell Line hCMEC/D3

Cells, Journal Year: 2023, Volume and Issue: 12(13), P. 1732 - 1732

Published: June 27, 2023

Nitric oxide (NO) represents a crucial mediator to regulate cerebral blood flow (CBF) in the human brain both under basal conditions and response somatosensory stimulation. An increase intracellular Ca2+ concentrations ([Ca2+]i) stimulates endothelial NO synthase produce cerebrovascular cells. Therefore, targeting ion channel machinery could represent promising strategy rescue signalling traumatic injury neurodegenerative disorders. Allyl isothiocyanate (AITC), major active constituent of cruciferous vegetables, was found CBF non-human preclinical models, but it is still unknown whether release capillary In present investigation, we showed that AITC evoked Ca2+-dependent cell line, hCMEC/D3. The shaped by intra- extracellular sources, although insensitive pharmacological blockade transient receptor potential ankyrin 1, which regarded be among main molecular targets AITC. accord, failed induce transmembrane currents or elicit membrane hyperpolarization, NS309, selective opener small- intermediate-conductance Ca2+-activated K+ channels, induced significant hyperpolarization. AITC-evoked signal triggered production cytosolic, not mitochondrial, reactive oxygen species (ROS), supported store-operated entry (SOCE). Conversely, did require mobilization from endoplasmic reticulum, lysosomes mitochondria. However, manipulation revealed AITC-dependent ROS generation inhibited plasma Ca2+-ATPase (PMCA) activity, thereby attenuating removal across resulting sustained [Ca2+]i. driven required ROS-dependent inhibition PMCA activity. These data suggest exploited restore disorders feature neurovascular dysfunction.

Language: Английский

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