Результаты поиска

The cardiovascular toxicity induced by high doses of gatifloxacin and ciprofloxacin in zebrafish.

As a new type of pollutant, fluoroquinolones (FQs) antibiotics are ubiquitous in environment and have some threat to human health and ecolog … cardiovascular toxicity in zebrafish, we investigated the transcriptional level of genes related to calcium signaling pathway and cardiac muscle contraction. The results indicated that the expression of ATPase (atp2a1l) and cardiac troponin C (tnnc1a) genes were significantly inhibited, the expression of calcium channel (cacna1ab) gene showed slight promoted trend …

Bone Morphogenetic Proteins 2/4 Are Upregulated during the Early Development of Vascular Calcification in Chronic Kidney Disease.

Vascular calcification is a main cause of increased cardiovascular morbidity and mortality in chronic kidney disease (CKD) patients. This study aimed to investigate the role of the bone morphogenetic protein (BMP) signaling pathway in the early development of vascular calcification in CKD. A CKD vascular calcification rat model was established by providing rats with a 1.8% high-phosphorus diet and an intragastric administration of 2.5% adenine suspension. The kidney and aortic pathologies were analyzed. Blood biochemical indicators, serum BMP-2 and BMP-4 levels, and aortic calcium content were

Proteomic analysis of imatinib-resistant CML-T1 cells reveals calcium homeostasis as a potential therapeutic target.

Chronic myeloid leukemia (CML) therapy has markedly improved patient prognosis after introduction of imatinib mesylate for clinical use. How … ocesses and tested their relative toxicity to CML-T1 and CML-T1/IR cells. Calcium channel blockers, calcium signaling antagonists and modulators of calcium homeostasis, namely thapsigargin, ionomycin, verapamil, carboxyamidotriazole and immunosuppressive drugs cyclosporine A and tacrolimus (FK-506) were selectively toxic to CML-T1/IR cells. The putative cellular ta …

Nickel suppresses the PACAP-induced increase in guinea pig cardiac neuron excitability.

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a potent intercellular signaling molecule involved in multiple homeostatic functions. PACAP/PAC1 receptor signaling increases excitability of neurons within the guinea pig cardiac ganglia, making them a unique system to establish mechanisms underlying PACAP modulation of neuronal function. Calcium influx is required for the PACAP-increased cardiac neuron excitability, although the pathway is unknown. This study tested whether PACAP enhancement of calcium influx through either T-type or R-type channels contributed to the modulation o

Estrogen and the Ca2+-mobilizing agonist ATP evoke acute NO synthesis via distinct pathways in an individual human vascular endothelium-derived cell.

In this study, we have systematically evaluated the signaling mechanisms underlying stimulated nitric oxide (NO) synthesis by estrogen (E2) and other vasoactive agents at the level of a single endothelium-derived cell. To do so, we have characterized and contrasted rapid E2-evoked NO synthesis with that of ATP using single-cell microfluorimetry and patch-clamp recordings to monitor stimulated changes in cellular NO synthesis (via 4-amino-5-methylamino-2',7'-difluorofluorescein), Ca2+ transients (via Fluo-3), and membrane hyperpolarization in cultured human EA.hy926 cells. E2-evoked NO synthesi

D1/D5 dopamine receptors stimulate intracellular calcium release in primary cultures of neocortical and hippocampal neurons.

D1/D5 dopamine receptors in basal ganglia, hippocampus, and cerebral cortex modulate motor, reward, and cognitive behavior. Previous work with recombinant proteins revealed that in cells primed with heterologous G(q/11)-coupled G-protein-coupled receptor (GPCR) agonists, the typically G(s)-linked D1/D5 receptors can stimulate robust release of calcium from internal stores when coexpressed with calcyon. To learn more about the intracellular signaling mechanisms underlying these D1/D5 receptor regulated behaviors, we explored the possibility that endogenous receptors stimulate internal release o

Presenilins, the endoplasmic reticulum, and neuronal apoptosis in Alzheimer's disease.

Many cases of autosomal dominant inherited forms of early-onset Alzheimer's disease are caused by mutations in the genes encoding presenilin … evels of oxidative stress. Recent studies of apoptosis in many different cell types suggest that ER calcium signaling can modulate apoptosis. The evolving picture of PS roles in neuronal plasticity and Alzheimer's disease is bringing to the forefront the ER, an organelle increasingly recognized as a key regulator of neuronal plasticity and survival.

Mitochondrial oxidative stress in skeletal muscle alters metabolic signaling responses to acute muscle contraction.

Activation of redox-sensitive signal transduction cascades is an increasingly appreciated mechanism of exercise adaptation in skeletal muscl … urbation in controls. Controls show pathway activation of insulin signaling and glucose metabolism, calcium signaling, and energy stress signaling processes compared to no activation in KD muscle. These results indicate that chronic mitochondrial redox stress shifts acute signaling responses away from metabolic signaling pathways and toward oxidative stress and apo …

Анализ воздействия тироида Хормоне на спинномозговые клетки.

Сигнал тироидного гормона (TH) регулирует клеточный метаболизм и реакцию стресса в сетчатке. Повышение уровня ТЗ в обращении связано с более высоким уровнем дегенерации, связанной с возрастом. Кроме того, стимуляция сигнала TH вызывает дегенерацию сетчатки у мышей, что сопровождается активацией клеток сетчатки. Здесь мы изучили транскрипционные изменения, вызванные трииодотиронином (T3) в сетчатых глиальных клетках с использованием одноклеточной последовательности RNA (scRNAseq) и биоинформатического анализа. Один месяц назад мышам C57BL/6 в течение четырех недель давали T3 (20 мкг/мл в питьев

Совпадение в аннотации оригинала
Thyroid hormone (TH) signaling regulates cellular metabolism and stress response in the retina. Increased TH levels in circulation are assoc … tes displayed downregulation of synaptogenesis, neurovascular coupling, cAMP response elements, and calcium signaling. Microglia showed upregulation of coordinated lysosomal expression and regulation signaling, systemic lupus erythematosus in T cells, and multiple sclerosis signaling, and downregulation of actin-binding Rho activating signaling, retinoic acid recep …

Activity of olive oil phenols on lymphomonocyte cytosolic calcium.

Phenols, present in the Mediterranean diet, have antioxidant properties and are free radical scavengers; however, the molecular mechanisms of their beneficial effects are not yet fully understood. The level of cytosolic calcium ([Ca2+]i) is an important signal also in nonexcitable cells, including immune cells, and regulates fundamental processes. In this paper, we determine [Ca2+]i in human lymphomonocytes incubated with two olive oil phenols: 3,4-(dihydroxyphenyl)ethanol and p-(hydroxyphenyl)ethanol. Both tested phenols increase [Ca2+]i in a dose-dependent way. This effect is antagonized by

The Ryanodine Receptor Contributes to the Lysophosphatidylcholine-Induced Mineralization in Valvular Interstitial Cells.

PURPOSE: Fibrocalcific aortic valve disease (CAVD) is caused by the deposition of calcific nodules in the aortic valve leaflets, resulting in progressive loss of function that ultimately requires surgical intervention. This process is actively mediated by the resident valvular interstitial cells (VICs), which, in response to oxidized lipids, transition from a quiescent to an osteoblast-like state. The purpose of this study was to examine if the ryanodine receptor, an intracellular calcium channel, could be therapeutically targeted to prevent this phenotypic conversion. METHODS: The expression

Presynaptic GABAA receptors control integration of nicotinic input onto dopaminergic axons in the striatum.

Axons of dopaminergic neurons express gamma-aminobutyric acid type-A receptors (GABAARs) and nicotinic acetylcholine receptors (nAChRs), which are positioned to shape striatal dopamine release. We examine how interactions between GABAARs and nAChRs influence dopaminergic axon excitability. Axonal patch-clamp recordings reveal that potentiation of GABAARs by benzodiazepines suppress dopaminergic axon responses to cholinergic interneuron transmission. In imaging experiments, we use the first temporal derivative of axonal calcium signals to distinguish between direct stimulation of dopaminergic a

Mutation in the auxiliary calcium-channel subunit CACNA2D4 causes autosomal recessive cone dystrophy.

Retinal signal transmission depends on the activity of high voltage-gated l-type calcium channels in photoreceptor ribbon synapses. We recently identified a truncating frameshift mutation in the Cacna2d4 gene in a spontaneous mouse mutant with profound loss of retinal signaling and an abnormal morphology of ribbon synapses in rods and cones. The Cacna2d4 gene encodes an l-type calcium-channel auxiliary subunit of the alpha (2) delta type. Mutations in its human orthologue, CACNA2D4, were not yet known to be associated with a disease. We performed mutation analyses of 34 patients who received a

S100A6 promotes liver metastasis by activating FGFR3 signaling in BAP1-deficient uveal melanoma.

Approximately 50% of uveal melanoma (UM) patients develop treatment-resistant liver metastases, surviving less than one year after diagnosis. While BRCA1-associated protein 1 (BAP1) deficiency strongly correlates with UM metastasis, its mechanistic role remains unclear. Through integrated analysis of four UM cohorts and functional experiments validation, we identified S100 calcium binding protein A6 (S100A6) as a key metastasis-associated gene consistently upregulated in BAP1-deficient UM. Mechanistically, BAP1 deficiency enhances H2AK119ub deposition and Pol II recruitment at the S100A6 promo

IL-4/Nanohydroxyapatite Codelivery in a Dual-Bionic Scaffold: Design and Immunomodulatory Endogenous Osteogenesis Mechanism.

Large-scale repairs of bone defects face the challenges of a dynamic extracellular matrix (ECM) signaling deficiency and mismatched hard-tis … stained nHA hydrolysis released Ca2+, synergizing with IL-10 and TGF-β to activate the PI3K-AKT and calcium signaling pathways, upregulating osteogenic and angiogenic markers. The results demonstrated the coupling mechanism between immunomodulation and osteogenic differentiation, presenting a strategy for promoting endogenous bone regeneration.

Intricacies of PKB/Akt Activity after Sciatic Nerve Damage: A Comprehensive Review.

Sciatic nerve injury represents a prevalent and incapacitating condition characterized by denervation, muscular atrophy, and compromised functionality. The Protein Kinase B (PKB)/ Akt signaling cascade serves as a vital modulator of skeletal muscle hypertrophy, metabolic processes, and regenerative capabilities. Subsequent to sciatic nerve injury, the PI3K/Akt signaling pathway exhibits dysregulation, exacerbating muscle atrophy and hindering recovery processes due to feedback inhibition of PKB/Akt phosphorylation by mTORC1, which consequently increases the expression of E3 ubiquitin ligases a

Sequential changes in calcium transients during M phase regulate cardiomyocyte proliferation.

Heart muscle growth and regeneration require the proliferation of cardiomyocytes. Rapid pulsatile increases in cytosolic Ca2+ concentration, called calcium transients (CaTs), trigger cardiomyocyte contractions, but how cardiomyocytes adapt Ca2+ signaling during proliferation is largely unknown. Here, we show that cardiomyocyte proliferation requires changes in Ca2+ signaling. Cardiomyocytes undergo a sequence of CaT changes during M phase: CaT amplitudes begin to decline in prometaphase, reach a minimum in metaphase, rise during anaphase, and return to the original state in daughter cardiomyoc

Coordinated cellular behavior regulated by epinephrine neurotransmitters in the nerveless placozoa.

Understanding how cells communicated before the evolution of nervous systems in early metazoans is key to unraveling the origins of multicel … ng more straightforward and efficient. Mechanistically, the binding of ligands activates downstream calcium signaling, subsequently modulating ciliary redox signals. This process ultimately regulates the beating direction of cilia, governing the coordinated movement of the organism. Our findings not only highlight the enduring presence of adrenergic signaling in st …

Unmasking the complex roles of hypocalcemia in cancer, COVID-19, and sepsis: Engineered nanodelivery and diagnosis.

Calcium (Ca2+) homeostasis is essential for maintaining physiological processes in the body. Disruptions in Ca2+ signaling can lead to various pathological conditions including inflammation, fibrosis, impaired immune function, and accelerated senescence. Hypocalcemia, a common symptom in diseases such as acute respiratory distress syndrome (ARDS), cancer, septic shock, and COVID-19, can have both potential protective and detrimental effects. This article explores the multifaceted role of Ca2+ dysregulation in inflammation, fibrosis, impaired immune function, and accelerated senescence, contrib

β-blockers augment L-type Ca2+ channel activity by targeting spatially restricted β2AR signaling in neurons.

G protein-coupled receptors (GPCRs) transduce pleiotropic intracellular signals in mammalian cells. Here, we report neuronal excitability of β-blockers carvedilol and alprenolol at clinically relevant nanomolar concentrations. Carvedilol and alprenolol activate β2AR, which promote G protein signaling and cAMP/PKA activities without action of G protein receptor kinases (GRKs). The cAMP/PKA activities are restricted within the immediate vicinity of activated β2AR, leading to selectively enhance PKA-dependent phosphorylation and stimulation of endogenous L-type calcium channel (LTCC) but not AMPA