Cell calcium最新文献

{"title":"Fura-10, unlike fura-2, is suitable for long-term calcium imaging in natural killer (NK) cells without compromising cytotoxicity and can be combined with target cell death analysis","authors":"Lea Kaschek ,&nbsp;Joanne Vialle ,&nbsp;Gebhard Stopper ,&nbsp;Markus D.A. Hoffmann ,&nbsp;Sylvia Zöphel ,&nbsp;Johanna Jansky ,&nbsp;Nadja Küchler ,&nbsp;Gertrud Schäfer ,&nbsp;Alina Moter ,&nbsp;Philipp Wendel ,&nbsp;Frank Neumann ,&nbsp;Claudia Schormann ,&nbsp;Evelyn Ullrich ,&nbsp;Leticia Prates Roma ,&nbsp;Carsten Kummerow ,&nbsp;Lorenz Thurner ,&nbsp;Eva C. Schwarz ,&nbsp;Markus Hoth","doi":"10.1016/j.ceca.2025.103091","DOIUrl":"10.1016/j.ceca.2025.103091","url":null,"abstract":"<div><div>There are compelling reasons to opt for primary human natural killer (NK) cells when validating Ca²⁺ indicators. 1.) NK cells exhibit a high degree of vulnerability to stressors such as indicator loading or light exposure. 2.) The lack of research on NK Ca²⁺ signaling underscores the necessity for developing reliable assays. 3.) The increased utilization of NK cell therapies necessitates a more profound comprehension of Ca²⁺ dependent signal transduction. Consequently, an assay was developed to monitor cytosolic Ca²⁺ signals in individual NK cells simultaneously with their cytotoxic function against cancer cells. We used this assay to assess the suitability of fura-2, fura-PE3, fura-8, fura-10 or fura-red for quantifying Ca²⁺ signals in NK cells without compromising their cytotoxic function. In contrast to the widely used fura-2, its red-shifted derivative fura-10 did not interfere with NK cytotoxicity over several hours. It exhibited a superior signal-to-noise ratio and good dynamic range, accompanied by minimal bleaching or leakage. Fura-8 and fura-red also preserved NK cell cytotoxicity, but had other disadvantages compared to fura-10. We successfully used fura-10 to report Ca²⁺ signals in NK cells from blood donors and patients diagnosed with lymphoma and leukemia over several hours at 37 °C during apoptotic or necrotic killing of different cancer cells (K562, THP1, OCI-AML2, and TMD8). Additionally, we show that fura-10 is well suited to report Ca²⁺ signals in intact murine pancreatic islets, another stress-sensitive cell preparation. Consequently, fura-10 is an optimal choice for measuring Ca²⁺ in primary human NK cells and other primary cell preparations.</div></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"133 ","pages":"Article 103091"},"PeriodicalIF":4.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145600390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nuclear Ca2+-Calmodulin signaling in cardiac myocytes reduces catecholamine-evoked protein translation and prevents hypertrophy","authors":"Anja Riedel ,&nbsp;Rebekka Medert ,&nbsp;Sara Monaco ,&nbsp;Enio Gjerga ,&nbsp;Xenia Tolksdorf ,&nbsp;Christin Richter ,&nbsp;Michelle Malz ,&nbsp;Meike Schrader ,&nbsp;Vladimir Kuryshev ,&nbsp;Martin Busch ,&nbsp;Andreas Jungmann ,&nbsp;Zoe Löwenthal ,&nbsp;Koenraad Philippaert ,&nbsp;Angela Wirth ,&nbsp;Roger Ottenheijm ,&nbsp;Vladimir Benes ,&nbsp;Patrick Most ,&nbsp;Christoph Dieterich ,&nbsp;Mirko Völkers ,&nbsp;Hilmar Bading ,&nbsp;Marc Freichel","doi":"10.1016/j.ceca.2025.103101","DOIUrl":"10.1016/j.ceca.2025.103101","url":null,"abstract":"<div><div>Cardiac remodeling, including hypertrophy, is associated with alterations in cytosolic Ca²⁺ homeostasis of cardiac myocytes that spill over into the nucleoplasm. To test whether nuclear Ca²⁺ signaling acts causally on the development of cardiac hypertrophy, we expressed parvalbumin to buffer nuclear Ca²⁺ and we blocked nuclear Ca²⁺-calmodulin signaling by Adeno-associated virus (AAV)-mediated expression of the calmodulin (CaM) binding-peptide nlsCaMBP4, respectively, in the nuclei of ES cell-derived (Cor.At) and neonatal rat ventricular cardiac myocytes (NRVCM). Expression of nlsCaMBP4, but not parvalbumin, leads to a significant reduction of hypertrophic growth induced by phenylephrine (PE). Expression of nlsCaMBP4 did not alter the amplitude of electrically-evoked intracellular Ca²⁺ transients in NRVCMs in the absence or presence of PE, and did not affect the PE-evoked increase in store-operated Ca²⁺ entry. Transcriptome analysis on NRVCMs expressing nlsCaMBP4 revealed that induction of classical hypertrophy markers such as ANF and BNP or MEF2 target genes (such as Srpk3, Xirp1 and Xirp2) were not reduced by nlsCaMBP4 expression. Further analysis of the nuclear Ca²⁺-calmodulin-regulated gene pool revealed differential expression of genes involved in mRNA translation, including the translation initiation factor subunits Eif2s1, Eif3d and Eif5, whose upregulation was absent in nlsCaMBP4-treated myocytes. Puromycin assays showed that inhibition of Ca²⁺-calmodulin signaling prevented catecholamine-evoked protein translation, suggesting that Ca²⁺-calmodulin signaling in the nucleus of cardiac myocytes regulates translation via transcriptional control mechanisms. However, future studies are needed to identify the exact molecular components and machinery that integrate Ca²⁺-calmodulin-dependent regulation of transcription, protein translation, and development of cardiac myocyte hypertrophy.</div></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"133 ","pages":"Article 103101"},"PeriodicalIF":4.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145733565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Orai1 plays a critical role in Orai3 synthesis and stability in luminal breast cancer cells","authors":"Alvaro Macias-Diaz ,&nbsp;Joel Nieto-Felipe ,&nbsp;Sandra Alvarado ,&nbsp;Francisco J. Martin-Romero ,&nbsp;Gines M. Salido ,&nbsp;Isaac Jardin ,&nbsp;Tarik Smani ,&nbsp;Jose J. Lopez ,&nbsp;Juan A. Rosado","doi":"10.1016/j.ceca.2025.103089","DOIUrl":"10.1016/j.ceca.2025.103089","url":null,"abstract":"<div><div>Orai family members are the pore-forming subunits of the Ca²⁺ release-activated Ca²⁺ (CRAC) channels that mediate store-operated Ca²⁺ entry (SOCE), a major mechanism for Ca²⁺ influx controlled by the filling state of the intracellular Ca²⁺ stores, that regulates a variety of cellular processes. While Orai1 plays a predominant role in SOCE, in luminal breast cancer cells, such as the MCF-7 cell line, SOCE is strongly dependent on Orai3. Using Orai1-knockout (KO) MCF-7 cells or silencing the expression of Orai1 by RNAi in wild-type MCF-7 or T47D cells we show that Orai1 plays a relevant functional role in the regulation of Orai3 expression, thus influencing SOCE. Transfection of Orai1-KO MCF-7 cells with Orai1α expression plasmid induces recovery of Orai1α that initially is not associated to changes in Orai3 protein levels or SOCE but after 7 days results in recovery of Orai3 protein content and SOCE. In Orai1-deficient MCF-7 cells, Orai3 protein synthesis was found to be attenuated, while Orai3 endo-lysosomal degradation was enhanced. Furthermore, Orai1 regulates the expression of estrogen receptor alpha (ERα), which has been associated to Orai3 expression in luminal breast cancer cells. Orai1 induces NFAT2 nuclear translocation in MCF-7 cells and NFAT2 overexpression attenuates ERα and Orai3 protein content in cells expressing Orai1. Our findings show that Orai1 is functionally associated with sustaining Orai3 synthesis and stability and ERα expression in luminal breast cancer cells, consequently modulating the ERα-Orai3 axis, rather than acting as a primary SOCE component.</div></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"132 ","pages":"Article 103089"},"PeriodicalIF":4.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145412535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LETM1 and mitochondrial calcium homeostasis: A controversial but critical role in cellular function and disease","authors":"Guilherme Rodrigo RM dos Santos ,&nbsp;Maiara Ingrid Cavalcante Queiroz ,&nbsp;Ana Catarina Rezende Leite","doi":"10.1016/j.ceca.2025.103085","DOIUrl":"10.1016/j.ceca.2025.103085","url":null,"abstract":"<div><div>Calcium is a pivotal ion in cellular signaling, orchestrating pathways that support both cell survival and cell death. The mitochondria and endoplasmic reticulum are the principal organelles responsible for Ca²⁺ storage and play fundamental roles in maintaining intracellular Ca²⁺ homeostasis. The mitochondrial outer membrane (MOM) acts as a selective barrier that regulates the exchange of metabolites and other essential molecules necessary for mitochondrial function. This tightly regulated exchange depends on specific proteins, such as the voltage-dependent anion channel (VDAC), which serves as a key mediator of metabolite flux across the MOM. The mitochondrial Ca²⁺ uniporter (MCU) and the electrogenic Na⁺/Li⁺/Ca²⁺ exchanger (NCLX) represents the best-characterized mechanisms governing mitochondrial Ca²⁺ uptake and efflux, respectively. The leucine zipper EF-hand–containing transmembrane protein 1 (LETM1), localized to the inner mitochondrial membrane (IMM), has also been implicated in the regulation of mitochondrial Ca²⁺ homeostasis. This IMM protein was initially identified in association with Wolf–Hirschhorn Syndrome (WHS), a rare chromosomal disorder characterized by microcephaly, growth retardation, intellectual disability, and early-onset epileptic seizures. Approximately sixteen years ago, LETM1 was proposed to mediate K⁺/H⁺ exchange across the IMM. However, subsequent studies suggested an alternative function as a Ca²⁺/H⁺ exchanger, leading to an ongoing debate regarding its exact physiological role. Despite this controversy, the crucial contribution of LETM1 to mitochondrial physiology is widely acknowledged. LETM1 is considered an essential gene, and its dysfunction has been associated with a spectrum of pathological conditions, including Parkinson’s disease, obesity, and cancer.</div></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"132 ","pages":"Article 103085"},"PeriodicalIF":4.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145358128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transglutaminase 2 controls calcium dependent mitochondrial dysfunction and fibroblast senescence by repressing PIEZO2","authors":"Jiaxiao Chen ,&nbsp;Geyan Tian ,&nbsp;Ming Hua ,&nbsp;Min Gu ,&nbsp;Wentao Sun ,&nbsp;Jingyi Xu ,&nbsp;Changjiao Luan ,&nbsp;Juping Chen ,&nbsp;Jiaxin Shi ,&nbsp;Yinsong Chen ,&nbsp;Xingjie Ma","doi":"10.1016/j.ceca.2025.103088","DOIUrl":"10.1016/j.ceca.2025.103088","url":null,"abstract":"<div><div>Calcium and intracellular calcium signaling have emerged as critical mediators of cellular senescence. However, the mechanisms by which calcium signaling participates in the regulation of senescence remain only partially understood. In this study, we identified that Transglutaminase 2 (TGM2) is remarkably upregulated in response to senescence stimuli. Furthermore, TGM2 overexpression accelerated fibroblast senescence, as evidenced by the upregulation of p16, p21, increased senescence associated β-galactosidase (SA-β-Gal) activity, decreased cell proliferative capacity and induction of senescence-associated secretory phenotype (SASP), whereas the silencing of TGM2 staved off the senescent phenotype of fibroblasts induced by therapy. Mechanistically, TGM2 facilitates mitochondrial calcium accumulation, thereby contributing to mitochondrial dysfunction, activation of cGAS-STING signaling and ultimately leading to fibroblast cellular senescence. Furthermore, RNA-sequencing of senescent cells containing siRNA control or siRNA against TGM2 revealed that TGM2 triggers fibroblast senescence by repressing mechanosensitive ion channel PIEZO2. Interestingly, knockdown of PIEZO2 counteracted the effect of TGM2 repression on inhibiting cGAS-STING signaling and delaying cellular senescence. Taken together, our findings demonstrate that TGM2 serves as a key regulator of fibroblast senescence by modulating calcium dependent mitochondrial dysfunction and provide potential therapeutical targets for combating aging process and age-associated disorders.</div></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"132 ","pages":"Article 103088"},"PeriodicalIF":4.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145358126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulation of actin cytoskeleton by Ca2+-binding S100 proteins","authors":"Ewelina Jurewicz ,&nbsp;Joanna Moraczewska ,&nbsp;Anna Filipek","doi":"10.1016/j.ceca.2025.103087","DOIUrl":"10.1016/j.ceca.2025.103087","url":null,"abstract":"<div><div>The actin cytoskeleton is a dynamic network present in all eukaryotic cells. It plays a central role in various cellular processes, including cell shape maintenance, motility, intracellular transport, and cell division. The actin cytoskeleton consists of actin filaments and a diverse array of associated actin-binding proteins (ABPs), which regulate the assembly, organization, and functions of actin filaments. S100 proteins, a family of low-molecular-weight Ca²⁺-binding proteins, have emerged as important regulators of actin filaments. They exert their regulatory functions either directly, through interactions with actin and actin-binding proteins (ABPs), or indirectly, by modulating Ca²⁺ release and thereby influencing actin-dependent contractility. This review article provides a comprehensive overview of current literature on the S100-dependent regulation of actin cytoskeleton dynamics in diverse cellular contexts. Specifically, it highlights the role of S100 proteins in modulating striated muscle contractility, actin–myosin interactions in smooth muscle, mechanotransduction, stress fiber assembly, lamellipodia formation, actin cortex organization, and structural organization of the actin cytoskeleton within synapses.</div></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"132 ","pages":"Article 103087"},"PeriodicalIF":4.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145399957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endothelial PIEZO1 activation impairs osteogenesis via GREM1-mediated inhibition of BMP signaling","authors":"Haoran Zhang ,&nbsp;Bowen Wang ,&nbsp;Jing He ,&nbsp;Shengyi Zhou ,&nbsp;Juan Song ,&nbsp;Ziwen Liu ,&nbsp;Xiangyu Zeng ,&nbsp;Ying Xing ,&nbsp;Feng Guo ,&nbsp;Jianyu Liu","doi":"10.1016/j.ceca.2025.103084","DOIUrl":"10.1016/j.ceca.2025.103084","url":null,"abstract":"<div><h3>Aim</h3><div>To investigate the effects and underlying mechanisms of systemic PIEZO1 activation on the bone vasculature and osteogenesis.</div></div><div><h3>Methods</h3><div>Three-week-old C57BL/6J male mice were intraperitoneally injected with Yoda1, and changes in bone microstructure and vasculature were assessed via micro-CT and immunofluorescence. MC3T3-E1 osteoprogenitors and endothelial cells (human umbilical vein endothelial cells, HUVECs and human bone marrow microvascular endothelial cells, hBMECs) were treated with Yoda1 in vitro. Gene expression analysis, alkaline phosphatase (ALP) assays, and RNA sequencing were performed to assess osteogenic activity and endothelial identity, respectively. Alterations in the osteogenic-promoting function of endothelial cells upon PIEZO1 activation were evaluated by treating MC3T3-E1 cells with endothelial-conditioned media.</div></div><div><h3>Results</h3><div>Systemic Yoda1 administration reduced the abundance of CD31^hiEMCN^hi-type H vessels and disrupted trabecular bone microarchitecture. Yoda1 suppressed osteogenic gene expression and ALP activity in MC3T3-E1 cells, even at low concentrations. RNA-seq of Yoda1-treated hBMECs revealed a transcriptional shift toward an <span>l</span>-type endothelial phenotype and upregulation of the expression of BMP antagonists, including GREM1. Functional rescue assays confirmed that endothelial-derived GREM1 inhibits BMP4-induced osteogenic differentiation via paracrine signaling.</div></div><div><h3>Conclusion</h3><div>Our study reveals a dual role of PIEZO1 in bone biology, demonstrating that its activation disrupts vascular–osteogenic coupling and suppresses osteoblast differentiation through the PIEZO1–GREM1–BMP4 axis. These findings suggest that caution should be taken when targeting PIEZO1 for bone regeneration and highlight the importance of dose and duration in therapeutic applications.</div></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"132 ","pages":"Article 103084"},"PeriodicalIF":4.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145358127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CNO induced Ca2+ store and glutamate-dependent nonspecific Ca2+ signalling in DREADD-free brain slices","authors":"Xiao-Yu Zhang ,&nbsp;Xi Wu ,&nbsp;Rui-yun Bi ,&nbsp;Shan Zhang ,&nbsp;Ye-Hua Gan","doi":"10.1016/j.ceca.2025.103070","DOIUrl":"10.1016/j.ceca.2025.103070","url":null,"abstract":"<div><div>DREADD (design receptors exclusively activated by designer drugs) is a widely used powerful tool designed to study specific cellular functions. However, off-target effects of chemogenetic activators, including clozapine N-oxide (CNO) and deschloroclozapine (DCZ), have been reported. In our study, we demonstrated the direct off-target effects of CNO and DCZ on basal Ca²⁺ levels in the locus coeruleus nucleus in both neurons and astrocytes by combining viral microinjection, Ca²⁺ imaging and electrophysiology. We observed that CNO induced a Ca²⁺ store-dependent increase in basal Ca²⁺ in both DREADD-absent neurons and astrocytes; interestingly, CNO directly increased the frequency of spontaneous presynaptic glutamate release. Furthermore, ionotropic glutamate receptors contributed to the CNO-induced increase in Ca²⁺ in both DREADD-free neurons and astrocytes. Importantly, IP3R2-KO diminished CNO-induced Ca²⁺ raise in astrocytes but not neurons. Our results revealed direct Ca²⁺ store- and glutamate-dependent off-target effects of DREADD agonists during their cellular action, which may help elucidate the mechanisms underlying the off-target effects of chemogenetic tools.</div></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"132 ","pages":"Article 103070"},"PeriodicalIF":4.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144922709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dantrolene normalizes heightened Ca2+ influx in activated T cells from the familial Alzheimer's disease TgF344-AD rats","authors":"Navdeep K. Uppal ,&nbsp;Anthony Valenzuela ,&nbsp;Pamela J. Lein ,&nbsp;Alla F. Fomina","doi":"10.1016/j.ceca.2025.103072","DOIUrl":"10.1016/j.ceca.2025.103072","url":null,"abstract":"<div><h3>Aim</h3><div>Dysregulation of the peripheral immune response contributes to Alzheimer's disease pathogenesis. Dantrolene, a negative allosteric modulator of ryanodine receptor types 1 and 3, reduces neurodegeneration in Alzheimer's disease animal models by an unclear mechanism. Given that Alzheimer's disease causative mutations in amyloid precursor and presenilin proteins interfere with intracellular Ca²⁺ signaling in neurons, we tested the hypotheses that these mutations may impair Ca²⁺ signaling in T lymphocytes and that dantrolene can repair this defect.</div></div><div><h3>Methods</h3><div>We explored cytosolic Ca²⁺ dynamics and effects of dantrolene sodium in resting and activated splenic T cells derived from adult transgenic TgF344-AD rats expressing mutant human \"Swedish\" amyloid precursor (APPsw) and presenilin 1 lacking exon 9 (PS1Δ9) proteins, and in control wild-type rats.</div></div><div><h3>Results</h3><div>We found no differences in the cytosolic Ca²⁺ signaling between resting T cells from TgF344-AD and control rats. In contrast, amplitudes of caffeine-triggered calcium transients and store-operated Ca²⁺ entry were significantly larger in activated TgF344-AD rat T cells relative to wild-type rat T cells. Preincubation with dantrolene sodium reduced the amplitude and the rate of Ca²⁺ influx in activated TgF344-AD rat T cells in the absence of store refilling and after dissipation of inner mitochondrial membrane potential, indicating that it does not involve Ca²⁺ release via ryanodine receptors or mitochondrial Ca²⁺ uptake.</div></div><div><h3>Conclusions</h3><div>Expression of Alzheimer's disease risk genes upregulates the store-operated Ca²⁺ entry in T cells, which may alter peripheral immune responses and exacerbate Alzheimer's disease pathogenesis. We speculate that dantrolene's neuroprotective effect in Alzheimer's disease animal models may be due to its normalization of the peripheral T cells' Ca²⁺ signaling and functions.</div></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"132 ","pages":"Article 103072"},"PeriodicalIF":4.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145045742","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Calcium homeostasis in trypanosomatids: A review of molecular targets and inhibitors","authors":"Natália Caroline Costa Coelho ,&nbsp;Angela Maria Arenas Velásquez ,&nbsp;Jhonatan Santos de Lima ,&nbsp;Ana Laura Dias Ramos ,&nbsp;Eduardo Maffud Cilli ,&nbsp;Marcia A.S. Graminha","doi":"10.1016/j.ceca.2025.103086","DOIUrl":"10.1016/j.ceca.2025.103086","url":null,"abstract":"<div><div>Calcium ion (Ca²⁺) signaling plays a pivotal role in the survival, differentiation, and virulence of trypanosomatids, including <em>Leishmania</em> spp., <em>Trypanosoma brucei</em>, and <em>Trypanosoma cruzi</em>, making it an attractive therapeutic target. This review integrates current knowledge on Ca²⁺ homeostasis in these parasites, addressing the plasma membrane, endoplasmic reticulum (ER), acidocalcisomes, mitochondria, lysosomes, and other organelles, with particular emphasis on key transporters and signaling pathways. In addition, we summarize genetic and pharmacological strategies used to validate Ca²⁺-related targets and highlight recent advances in both repurposed and novel compounds that disrupt Ca²⁺ homeostasis in trypanosomatids.</div></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"132 ","pages":"Article 103086"},"PeriodicalIF":4.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145400018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}