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At least 19 recordsLinked to original sources
PubMed2026

CaCl2 Priming Boosts Salinity-Alkalinity Tolerance in Germinating Soybean by Reducing DNA Oxidative Damage and Enhancing Ca2+ -ROS Signaling Crosstalk.

Soybean (Glycine max) seed germination is highly sensitive to saline-alkaline stress. Seed priming represents an effective strategy to mitigate its detrimental effects. However, the optimal priming conditions (agent, concentration, duration) and the underlying molecular mechanisms remain poorly understood. This study investigated the effects of priming with distilled water (Control), calcium chloride (CaCl2), melatonin (MT), and proline (Pro) under saline-alkaline stress on soybean seed germination and the molecular basis of enhanced tolerance. Evaluation of ten germination-related parameters revealed that priming with 100 mM CaCl2 for 12 h significantly enhanced the germination rate. Physiological analyses demonstrated that CaCl2 priming effectively reduced reactive oxygen species (ROS) accumulation by increasing the activities of superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT), while decreasing malondialdehyde (MDA) content. Furthermore, CaCl2 priming activated the Ca2+ signaling pathway by increasing radicle Ca2+ content and upregulating the expression levels of Ca2+ signaling-related genes (e.g., GmCAM7, GmCNGC2, GmCNGC19, GmMPK2, and GmMKK2). Additionally, CaCl2 priming significantly enhanced DNA damage repair capacity of soybean cultivars with differing saline-alkaline tolerance. This was manifested by reduced DNA oxidative damage and decreased random amplified polymorphic DNA (RAPD) polymorphism, thereby enhancing genomic stability and alleviating cell cycle arrest. These findings deepen our understanding of the complex regulatory role of calcium signaling in plant abiotic stress responses and provide important novel theoretical insights for improving crop resilience.

Glycine max↗
PubMed2026

Intermembrane coupling between Bcl-xL and the IP3 receptor supports local Ca2+ transfer at ER-mitochondrial contacts.

Bcl-xL, an anti-apoptotic Bcl-2 family protein, engages laterally with Bak/Bax in the outer mitochondrial membrane (OMM) to inhibit apoptosis and interacts with the IP3 receptor Ca2+ channels (IP3Rs) in the endoplasmic reticulum (ER) membrane to control Ca2+ release. It is unknown if OMM-localized Bcl-xL can also interact in trans with IP3Rs at ER-mitochondrial contacts to form a tethering complex that supports IP3R-mediated local Ca2+ transfer from ER to mitochondria. We establish that IP3R-mitochondria Ca2+ signal propagation depends on Bcl-xL. By targeting Bcl-xL specifically to different subcellular compartments, we find that OMM-localized Bcl-xL increases the efficacy of ER-mitochondrial Ca2+ transfer without changing ER Ca2+ release, despite attenuating mitochondrial Ca2+ uptake. We find interaction between Bcl-xL and each IP3R isoform occurring at the mitochondria and a complex formed by OMM-localized Bcl-xL and IP3Rs. OMM Bcl-xL interacts with IP3Rs in trans at ER-mitochondrial contacts to optimize local Ca2+ signal propagation into the mitochondria.

Bcl-xL↗
PubMed2025

Membrane potential and feedback dynamics regulate CatSper-mediated progesterone signaling in human sperm.

Activation of the sperm-specific Ca2+ channel CatSper by progesterone evokes rapid changes in intracellular Ca2+ in human sperm that are required for fertilization. However, the mechanisms regulating the progesterone-induced Ca2+ signals have remained elusive. Here, we used quantitative kinetic fluorimetry with fast voltage-sensitive fluorescent indicators to investigate how progesterone affects the membrane potential (Vm) of human sperm. Additionally, we employed the FASTM technique to simultaneously record at millisecond time resolution changes in both Vm and intracellular Ca2+. We show that progesterone evokes a rapid pulse-like depolarization and repolarization. The depolarization is caused by Ca2+ influx through CatSper, which pulls Vm away from a resting membrane potential (Vrest) of -65 mV set by the sperm-specific K+ channel Slo3. We further show that Vm- and Ca2+-dependent mechanisms limit the CatSper-mediated Ca2+ influx, thereby promoting repolarization and enabling K+ efflux through Slo3 channels to restore Vrest. Our findings demonstrate that non-genomic progesterone signaling in human sperm is regulated by negative feedback on CatSper and involves a dynamic interplay between CatSper and Slo3 in controlling Vm. We anticipate that our novel kinetic, quantitative Vm recording and Vm/Ca2+-multiplexing techniques will reveal additional molecular mechanisms underlying CatSper-mediated Ca2+ signaling in human sperm both in health and disease.

CatSper↗
PubMed2025

Loss of STIM1 and STIM2 in Salivary Glands Disrupts ANO1 Function but Does Not Induce Sjogren's Disease.

Ca2+ signaling via the store-operated Ca2+ entry (SOCE) mediated by STIM1 and STIM2 proteins and the ORAI1 Ca2+ channel is important in saliva fluid secretion and has been associated with Sjogren's disease (SjD). However, there are no studies addressing STIM1/2 dysfunction in salivary glands or SjD in animal models. We report that mice lacking Stim1 and Stim2 [Stim1/2K14Cre(+)] in salivary glands exhibited reduced Ca2+ levels and hyposalivate. SOCE was functionally required for the activation of the Ca2+ activated Cl- channel ANO1. Ageing Stim1/2K14Cre(+) mice showed no evidence of lymphocytic infiltration or increased levels of autoantibodies characteristic of SjD, possibly associated with a downregulation of toll-like receptor 8 (Tlr8) expression. Salivary gland biopsies of SjD patients showed increased expression of STIM1 and TLR7/8. Our study shows that SOCE activates ANO1 function and fluid secretion in salivary glands and highlights a potential link between SOCE and TLR signaling in SjD.

Stromal Interaction Molecule 1↗
PubMed2026

Development of receptor and oncogene-responsive luciferase reporter vectors that are activated via kinase signaling to AP-1.

This study aimed to generate lentiviral vectors carrying an array of AP-1 motifs driving luciferase gene expression as reporters of mitogen-activated protein kinase (MAPK) activity. We created a series of vectors based on LeGO-iG that were used to generate stably transduced leukemia cell lines. A vector termed LEGO-AP1×6-GM55 containing an array of 6 AP-1 sites linked to the minimal CSF2 promoter was sufficient to support high levels of MAPK-inducible luciferase activity in leukemic cell lines that was suppressed by MAPK inhibitors. The inclusion of a putative chromatin priming element encompassing RUNX and ETS motifs increased the activity of these vectors. The additional inclusion of the full-length mouse CSF2 promoter, or the human DUSP5 promoter further increased the MAPK-dependent activity of these vectors in leukemic cells. These vectors support moderate levels of constitutive activity in cells carrying mutations that activate the RAS/RAF/MEK MAPK signaling pathway, and high-level activity after direct activation of MAPK signaling. They also respond to T-cell receptor activation via MAPK and Ca2+ signaling pathways. This resource will now make it easier to track receptor or oncogene-inducible MAPK activity in cultured cells, and potentially in tumors, close to real-time.

Humans↗
PubMed2026

Acbd7 is essential for preserving hair cell-mediated auditory and vestibular function.

Understanding the molecular basis of hair cell function is essential for elucidating inner ear physiology and developing therapies for auditory-vestibular disorders. Here, we identify acyl-CoA binding domain-containing 7 (Acbd7) as a hair cell-specific gene critical for sensory maintenance. Single-cell transcriptomics of mouse cochlear organoids revealed Acbd7 as a top hair cell-enriched transcript, with its spatiotemporal expression confirmed from embryonic development through adulthood in both auditory and vestibular hair cells. Acbd7‑deficient mice exhibited pronounced hair cell degeneration, characterized by synaptic defects and diminished calcium currents in inner hair cells and loss of outer hair cells. Transcriptomic and proteomic analyses linked Acbd7 to the regulation of Ca2+ signaling and fatty acid metabolism pathways. Our findings establish Acbd7 as a critical regulator of Ca2+ homeostasis and functional integrity in hair cells, thereby elucidating a key mechanism by which a fatty acid metabolism factor sustains hair cell function and providing potential therapeutic targets for inner ear disorders.

Animals↗
PubMed2026

Redox Rewiring in Nicotine-Driven Gastric Carcinogenesis: Uncovering ROS-Dependent Oncogenic Circuits.

SIGNIFICANCE: Nicotine from tobacco products, secondhand smoke, and emerging delivery systems remains a major but underappreciated driver of gastric carcinogenesis (GC). Although reactive oxygen species (ROS) have long been implicated in tumor biology, current models incompletely explain how chronic nicotine selectively reprograms gastric epithelial signaling. This review advances the concept of redox rewiring, whereby nicotine establishes a persistent oxidative state that orchestrates multiple oncogenic programs via spatially compartmentalized NOX signaling. RECENT ADVANCES: We synthesize evidence for a unified model wherein nicotine activates nAChR/β-AR signaling, Ca2+ influx, PKC, and compartmentalized NOX-derived ROS to generate distinct oncogenic outputs. Beyond the established NOX/ROS/NF-κB/MAPK-driven IL-8 and MMP-9 axes, we integrate emerging evidence into three interconnected modules governing EMT/metastasis (ABL1/STAT3/COX-2/periostin), survival/chemoresistance (ERK/GLI1/Bcl-2), and invasion/immune evasion (miR-21/PDCD4). Collectively, these circuits suggest that ROS function not merely as damaging byproducts but as spatially organized signaling mediators dictating tumor behavior. CRITICAL ISSUES: A major challenge is distinguishing established mechanisms from incompletely validated models. The three proposed axes are testable hypotheses requiring experimental validation. Most data derive from in vitro studies with nonphysiologic nicotine concentrations, and artifacts from nonspecific ROS probes are common. Compensatory pathway activation and multi-target effects of natural products remain underexplored. FUTURE DIRECTIONS: We outline a precision-redox oncology roadmap linking pathway-specific biomarkers, mechanistically matched natural products, and biomarker-enriched trials. Priorities include genetic validation of the three axes, time-resolved ROS imaging, and pulsed natural product regimens. By reframing nicotine-driven GC as adaptive redox network remodeling, this review provides a framework for prevention, stratification, and next-generation therapy. Antioxid. Redox Signal. 00, 000-000.

gastric cancer↗
PubMed1979

Polarization of chlorotetracycline fluorescence in pancreatic islet cells and its response to calcium ions and D-glucose.

Suspensions rich in pancreatic beta-cells were prepared from non-inbred ob/ob-mice, incubated with 10 micrometer-chlorotetracycline, and analysed for fluorescence polarization in a microscope. Throughout the temperature range 16--38 degrees C, fluorescence was enhanced by 5 mM-Ca2+ in the incubation medium; 20 mM-D-glucose decreased the fluorescence measured in the presence of Ca2+. Fluorescence showed a curvilinear negative regression on temperature. The curves were rectified to a virtually ideal degree by Arrhenius transformations of data. Non-parametric testing of differences between linearized regression lines forms the basis for the following conclusions. The temperature-dependence of fluorescence intensity appeared to be smaller for Ca2+-specific signals than for the background fluorescence of chlorotetracycline in Ca2+-deficient cells. D-Glucose significantly diminished the polarization of fluorescence in cells incubated with Ca2+. It is suggested that D-glucose increases the mobility of Ca2+ in beta-cell plasma membranes; this mobility increase may help to explain previously reported effects of D-glucose on 45Ca2+ fluxes and membrane electric potential.

Animals↗
PubMed2024

Convergence on CaMK4: A Key Modulator of Autism-Associated Signaling Pathways in Neurons.

Although the precise underlying cause(s) of autism spectrum disorder remain unclear, more than 1000 rare genetic variations are associated with the condition. For many people living with profound autism, this genetic heterogeneity has impeded the identification of common biological targets for therapy development for core and comorbid traits that include significant impairments in social communication and repetitive and restricted behaviors. A substantial number of genes associated with autism encode proteins involved in signal transduction and synaptic transmission that are critical for brain development and function. CAMK4 is an emerging risk gene for autism spectrum disorder that encodes the CaMK4 (calcium/calmodulin-dependent protein kinase 4) enzyme. CaMK4 is a key component of a Ca2+-activated signaling pathway that regulates neurodevelopment and synaptic plasticity. In this review, we discuss 3 genetic variants of CAMK4 found in individuals with hyperkinetic movement disorder and comorbid neurological symptoms including autism spectrum disorder that are likely pathogenic with monogenic effect. We also comment on 4 other genetic variations in CAMK4 that show associations with autism spectrum disorder, as well as 12 examples of autism-associated variations in other genes that impact CaMK4 signaling pathways. Finally, we highlight 3 environmental risk factors that impact CaMK4 signaling based on studies of preclinical models of autism and/or clinical cohorts. Overall, we review molecular, genetic, physiological, and environmental evidence that suggest that defects in the CaMK4 signaling pathway may play an important role in a common autism pathogenesis network across numerous patient groups, and we propose CaMK4 as a potential therapeutic target.

Humans↗
PubMed2026

Allelochemical signaling and phytohormone crosstalk in plants: molecular mechanisms and implications for sustainable weed management.

Phytotoxic effects from allelopathy occur due to signaling pathways that induce alterations in hormonal balance within the plants, thereby hindering weed growth. Signaling crosstalk between various hormones and signaling pathways (Ca2⁺, MAPK, ROS) is involved in the molecular response mechanisms found through omics. Utilizing such mechanisms would help develop new environmentally friendly methods for sustainable weed management. Allelopathy serves as an essential component of plant-plant interaction via controlling the secretion of secondary metabolites (allelochemicals), which affect the growth, development, and physiological activity of nearby plants. The latest findings indicate that allelochemicals disturb phytohormone balance and signaling pathways resulting in oxidative stress, metabolism dysfunctions, cellular processes disturbances, and eventually inhibiting the growth of target weed species. Molecular biology progress and omics techniques brought information about the sophisticated regulation processes involved in allelopathic interactions. This review summarizes the information about the molecular mechanism of weed suppression mediated by allelopathy with the emphasis on allelochemical perception, phytohormone signaling, ROS responses, and evidence obtained by the application of transcriptomics, proteomics, metabolomics, and other omics-based studies. In addition, it introduces novel approaches, such as rhizosphere engineering, nanotechnologies, and genome editing, which may improve the effectiveness and reliability of allelopathic weed suppression. Overall, these achievements provide prospects for creating a new generation of weed control technologies that are sustainable, environmentally friendly, and climate-adaptive.

Plant Growth Regulators↗
PubMed2025

Molecular mechanisms and breeding strategies for heat tolerance in vegetable crops under global warming.

Extreme heat driven by climate change poses a catastrophic threat to global vegetable production, undermining nutritional security because of the heightened physiological sensitivity and succulent tissues of these crops. This review synthesizes the multistage impacts of heat stress across critical developmental phases-from germination to reproduction-emphasizing morphological impairments (such as leaf wilting and floral abortion) and physiological disruptions (including photosynthetic inhibition and oxidative damage). We systematically dissect thermotolerance mechanisms in vegetables, highlighting transcriptional reprogramming by HSFs, WRKY, and NAC transcription factors; chaperone-mediated proteostasis via HSPs; epigenetic remodeling; Ca2+-ROS signaling pathways; and the role of phase separation dynamics. Importantly, we propose six strategic pathways to develop heat-resilient vegetables: harnessing natural variation through pan-genome-driven allele mining; employing biotechnological interventions such as CRISPR-mediated editing and synthetic promoters; engineering multistress tolerance by targeting conserved 'core response' pathways; exploiting epigenetic memory to achieve transgenerational resilience; optimizing source-sink dynamics with ''Climate-Responsive Carbon Optimization; and applying plant growth regulators and nanotechnology to enhance thermotolerance. Together, these strategies chart a clear roadmap for climate-smart vegetable breeding and call for interdisciplinary collaboration to translate molecular discoveries into practical breeding approaches for sustainable food systems under escalating thermal extremes.

Journal Article↗
PubMed2026

Molecular and transcriptional regulation of plant defense responses to aphid infestation.

Aphids are one of the important agricultural pests causing substantial yield losses in crops grown across the globe. Aphids are known to cause direct feeding damages and indirect losses due to sooty mold development and plant virus transmission. Plants respond to these attacks by mounting a complex defense response at the infested sites and systemic levels. This multilayered defense response involves a highly coordinated network of phytohormones and other signalling components like Ca2+, mitogen activated protein kinases and reactive oxygen species. Key to these complex responses is a well-regulated gene expression involving several transcription factors. A wide range of transcription factors are structurally and functionally characterized across some model plants and in a few agronomically important crops. These transcription factors play diverse roles such as defense gene expression modulation, regulation of hormone signaling, secondary metabolism, oxidative stress response, cell wall modifications, and phloem-based defense. Understanding the integration of signaling pathways, hormone crosstalk, and transcription factor mediated regulation provides a framework for practical applications, including breeding, genome editing, and elicitor-based strategies. This review highlights how plant defense signaling and transcriptional regulation against aphids can be harnessed to develop sustainable and novel pest management solutions.

Aphid↗
PubMed1979

Dissociation of action potentials from contraction in single crab muscle fibers.

In single crab fibers (Callinectes danae) bathed in Ca2+-free media, Ba2+ action potentials did not elicit tension. In contrast, Sr2+ spikes evoked twitches similar in amplitude to those accompanying the control Ca2+ spikes. Tension development in these fibers, therefore, depends on the ionic species carrying the inward current during membrane excitation. The Ca2" or Sr2+ influx appears insufficient to evoke the observed twitch tensions, and it seems necessary to postulate mobilization of an intracellular source of Ca1+. Procaine, which suppresses release of Ca2+ from sarcoplasmic reticulum, depressed twitch tension but did not reduce the overshoot or duration of Ca2+ or Sr2+ spikes. This finding is compatible with the suggestion that the contractions results from release of Ca2+ from the sarcoplasmic reticulum initiated by signals given by the influx of Ca2+ or Sr2+, but not Ba2+.

Action Potentials↗
PubMed1978

Calcium transients in aequorin-injected frog cardiac muscle.

The Ca2+ -sensitive bioluminescent protein aequorin was microinjected into cells of frog atrial trabeculae to study intracellular calcium transients associated with excitation-contraction coupling. The amplitude of the aequorin signal increased with extracellular Ca2+ concentration and stimulus frequency, but decreased with stretch. Isoprenaline and acetylstrophanthidin both increased the amplitude, but had strikingly different effects on the time course of the signal.

Action Potentials↗
PubMed1978

Chlorotetracycline as a fluorescent Ca2+ probe in pancreatic islet cells.

Pancreatic islets, or suspensions of islet cells, from noninbred ob/ob-mice were incubated with chlorotetracycline and analyzed for Ca2+-dependent fluorescence in a microscope. Unless logarithmically transformed, signals from islets were asymmetrically distributed with unstable variance. Signals from cells pelleted in glass capillaries were more homogeneous and depended linearly on the thickness of the sample. The effect of sample thickness and a significant enhancement of fluorescence by alloxan suggest that beta-cells were involved in producing the signal from whole islets. The signal from dispersed cells was probably diagnostic of Ca2+ in beta-cell plasma membranes because it was suppressed by La3+ and had a spectrum indicative of an apolar micromilieu; fluorescent staining of cell surfaces was directly seen at high magnification. Fluorescence from cells was enhanced by 0.5-10 mM Ca2+ in a dose-dependent manner, whereas less than 0.5 mM Ca2+ saturated the probe alone in methanol. The signal from islets or dispersed cells was suppressed by 5 mM theophylline; that from cells was also suppressed by 0.5 mM 3-isobutyl-1-methylxanthine, 1.2 or 15 mM Mg2+, 3-20 mM D-glucose, and, to a lesser extent, 20 mM 3-O-methyl-D-glucose. D-glucose was more inhibitory in the absence than in the presence of Mg2+, as if Mg2+ and D-glucose influenced the same Ca2+ pool. L-glucose, D-mannopheptulose, or diazoxide had no noticeable effect and 20 mM bicarbonate was stimulatory. The results suggest that microscopy of chlorotetracycline-stained cells can aid in characterizing calcium pools of importance for secretion. Initiation of insulin release may be associated with an increas

Alloxan↗
PubMed1979

Computer simulation of metabolism in pyruvate-perfused rat heart. V. Physiological implications.

The results of a simulation of metabolism in the pyruvate-perfused rat heart subjected to a sudden increase in work load are interpreted to provide a coherent explanation for the observed physiology. Respiration is most closely correlated with the mitochondrial phosphate potential, calculated from the MgATP and MgADP levels. No correlation between respiration and the pH gradient across the mitochondrial membrane was found. The transient falls in pH in the cytosol and perhaps the mitochondria are due largely to carbonic and lactic acidosis and appear to be only weakly coupled. The heart maintains a high ATP level during the transition to increased work by utilizing its energy reserves in order of decreasing availability in response to physiological signals mediated by Mg2+, Ca2+, and cAMP.

Animals↗
PubMed1975

Conformational studies on parvalbumins by circular dichroism.

Structural variations of two parvalbumins, Whiting III and Pike III, in various denaturing conditions, have been studied by circular dichroism. CD signals are depressed from 4 urea. For Pike III, acidic pH, sodium dodecyl sulfate or complete removal of Ca2+ show little effect in the far ultraviolet region but rather strong effects in the near ultraviolet. For Whiting III similar results are obtained at acidic pH. Carboxymethylated Whiting III (0.15 Ca2+/mol) shows, on the contrary, decreased CD signals in the far and in the near ultraviolet spectra. Addition of Ca2+ fully restores the native CD spectra in both proteins. Ca2+ binding produces structural modifications which are found to vary according to parvalbumin and which seem in any case different from those described for troponin C.

Animals↗
PubMed2025

Dynamic phosphorylation of Hcm1 promotes fitness in chronic stress.

Cell survival depends upon the ability to adapt to changing environments. Environmental stressors trigger an acute stress response program that rewires cell physiology, downregulates proliferation genes and pauses the cell cycle until the cell adapts. After the acute response is resolved, cells resume cycling but at a reduced rate. The importance of cell cycle changes for survival in chronic stress is not clear. Here, we show that dynamic phosphorylation of the yeast cell cycle-regulatory transcription factor Hcm1 is required to maintain fitness in chronic stress. Hcm1 is activated by cyclin dependent kinase (CDK) during S-phase and is inactivated by the phosphatase calcineurin (CN) in response to stressors that signal through increases in cytosolic Ca2+. Cells expressing a constitutively active, phosphomimetic Hcm1 mutant exhibit a reduction in fitness in stress, suggesting Hcm1 inactivation promotes survival. However, a comprehensive analysis of Hcm1 phosphomutants revealed that Hcm1 activity is also important to survive stress, and that all mutants with fixed phosphorylation states are less fit in stress. Moreover, our data suggests that pulses of Hcm1 activity are necessary to maximize target gene expression in stress. These findings demonstrate that expression levels of Hcm1 target genes influence fitness in stress and suggest that the dynamic phosphorylation of cell cycle regulators plays a crucial role in promoting survival in stressful environments.

Phosphorylation↗