Ask about this productRelated genes to: ORAI1 antibody
- Gene:
- ORAI1 NIH gene
- Name:
- ORAI calcium release-activated calcium modulator 1
- Previous symbol:
- TMEM142A
- Synonyms:
- FLJ14466, CRACM1
- Chromosome:
- 12q24.31
- Locus Type:
- gene with protein product
- Date approved:
- 2006-04-10
- Date modifiied:
- 2019-04-23
Related products to: ORAI1 antibody
Related articles to: ORAI1 antibody
- : Intracellular Ca dysregulation and neurovascular dysfunction are increasingly recognized as important mechanisms underlying neurodegenerative disorders, including Alzheimer's disease (AD). Restoration of pathological Ca imbalance has therefore emerged as a potential therapeutic strategy. Although ginsenoside compound K (CK) has demonstrated neuroprotective and anti-inflammatory properties, its role in Ca homeostasis remains unclear. : SH-SY5Y neuronal cells, U373 astrocytes, BV2 microglia, bEND brain endothelial cells, and MOVAS vascular smooth muscle cells were exposed to trimethyltin chloride (TMT, 5 μM, 24 h). Cell viability, real-time cell confluence, intracellular Ca influx, and endoplasmic reticulum (ER) Ca store release were evaluated. Ca dynamics were analyzed using Fura-2 fluorescence, and signaling associated with CK-mediated Ca regulation was investigated using pharmacological inhibitors. Orai1 protein expression was evaluated by Western blot analysis in SH-SY5Y and U373 cells. : TMT increased store-operated Ca entry (SOCE)-mediated Ca influx in SH-SY5Y neuronal cells without significant cytotoxicity. In contrast, TMT reduced both Ca influx and cell viability in U373 astrocytes, BV2 microglia, and MOVAS cells, whereas bEND cells showed minimal changes. CK restored abnormal Ca responses in a cell type-specific manner, reducing elevated Ca influx in neuronal cells while restoring suppressed Ca signaling in astrocytes. Consistent with these functional findings, Orai1 protein expression was increased by TMT in SH-SY5Y cells and attenuated by CK, whereas TMT reduced Orai1 expression in U373 cells, which was restored by CK. Pharmacological analyses suggested involvement of PKA- and LTCC-associated signaling in neuronal cells and PLC- and PLD-associated signaling in astrocytes. In both cell types, CK-associated Ca responses were sensitive to NAC and the SOCE inhibitor BTP2, supporting ROS- and SOCE-associated mechanisms. Additional controls showed no significant inhibitor effects under control or CK-only conditions, strengthening the pharmacological interpretation of responses under TMT-containing conditions. : TMT-induced Ca dysregulation differed markedly by cell type. CK restored disrupted Ca homeostasis in association with distinct pharmacological signaling profiles in neuronal and astrocytic cells. These findings suggest that CK may function as a cell type-specific Ca homeostatic regulator under neurotoxic stress conditions and highlight the importance of differential Ca regulation in neurodegenerative disease models. - Source: PubMed
Publication date: 2026/08/31
Jeon HayeongKim Yoo JinSeol Geun Hee - ORAI channels are store-operated Ca channels, which play important roles in physiology and pathophysiology. ORAI channel modulators are useful for developing pharmacological interventions. Here, we aimed to investigate the benzhydryl-derived analogues as novel ORAI channel blockers. The effects of benzhydryl-derived analogues TH1177, clemastine, cloperastine, and diphenhydramine were investigated in HEK-293 cells overexpressing individual ORAI isoforms and STIM1. The ORAI currents were recorded by patch-clamp, and cytosolic Ca was measured by a fluorescent Ca dye. TH1177 inhibited ORAI1, ORAI2, and ORAI3 currents with IC values of 18.3 μM, 4.8 μM, and 35.6 μM, respectively. Clemastine inhibited ORAI1 and ORAI2, but showed no effect on ORAI3. Both cloperastine and diphenhydramine, without a pyrrolidine ring structure, only showed minimal inhibition of ORAI1. Intracellular application of TH1177 and outside-out patch demonstrated that TH1177 blocked ORAI3 currents via the extracellular surface. TH1177 did not affect cytosolic STIM1 clustering and movement. Moreover, TH1177 potently inhibited cell proliferation with IC values of 2.6 µM for HAEC, 5.2 µM for EA.hy926, and 29.4 µM for HK-2 cells and induced apoptotic cell death. It is concluded that TH1177 is a pan-inhibitor for ORAI1-3 channels, while clemastine inhibits ORAI1 and ORAI2 but shows little effect on ORAI3. The pyrrolidine ring structure in the compounds of TH1177 and clemastine is critical for their inhibitory activity. The two benzhydryl derivatives (cloperastine and diphenhydramine) without the pyrrolidine ring only showed minimal inhibition of ORAI1. Our findings give a new pharmacological profile of ORAI channels. - Source: PubMed
Publication date: 2026/09/21
Li PengyunRubaiy Hussein NHallett ThomasLiang YiChen Gui-LanZeng BoZheng PingpingZaibi NawelSu Dong-NaBoa Andrew NXu Shang-Zhong - Lysosomal Ca release can trigger endoplasmic reticulum (ER) Ca mobilisation, which would be expected to activate store-operated Ca entry (SOCE). Recent work by Lee et al. reveals that activation of the lysosomal two-pore channel TPC2 instead suppresses SOCE despite ER Ca depletion. TPC2-derived Ca signals recruit calmodulin to promote STIM1 inactivation, imparing STIM oligomerisation and coupling to Orai1. These findings identify a lysosomal feedback pathway that restrains Ca influx and expand the role of TPC2 from an initiator of intracellular Ca release to a brake on SOCE. - Source: PubMed
Publication date: 2026/09/22
Mu QianruPatel SandipYule DavidShetty Siddhi - Elevated circulating levels of fibroblast growth factor 23 (FGF23) are linked to arterial stiffness and cardiovascular risk, and blocking FGF23 has been proposed as a therapeutic strategy. However, whether FGF23 inhibition is beneficial or detrimental for vascular function remains unknown. - Source: PubMed
Publication date: 2026/09/24
García-Sáez Raquel MTorralbo-Romero Ana ILópez-Baltanás RodrigoRivas-Dominguez AntonioSerrano-Berzosa RafaelObrero TeresaValdes-Diaz KarenJurado-Montoya DanielGómez-Gómez EnriqueCampos-Hernandez Juan PLellig MichaelaJankowski VeraJankowski JoachimFernández-Tenorio MiguelLeiva-Cepas FernandoRodríguez-Ortiz María Ede Mier María V Pendón RuizRodríguez MarianoRodelo-Haad CristianMuñoz-Castañeda Juan R - The Ca release-activated Ca (CRAC) channel, triggered by the interaction between the Ca sensor STIM1 and Orai1, is the primary mediator of store-operated calcium entry (SOCE). Dysregulation of this process drives numerous human pathologies, particularly immune disorders and cancer hallmarks. Due to its role, Orai1 has emerged as an attractive target for precision therapeutics. - Source: PubMed
Publication date: 2026/09/21
Jardín IsaacMacias-Díaz AlvaroJimenez-Velarde VanesaFuentes-Mateos ManuelSmani TarikRosado Juan A