Involvement of Orai1 in tunicamycin-induced endothelial dysfunction

Yang, Hui; Xue, Yan; Kuang, Su‐Juan; Zhang, Mengzhen; Chen, Jinghui; Liu, Lin; Shan, Zhi‐Xin; Lin, Qiaoli; Li, Xiaohong; Zhou, Hui; Rao, Fang; Deng, Chunyu

doi:10.4196/kjpp.2019.23.2.95

Cited by 6 publications

(7 citation statements)

References 28 publications

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“…As a non-excitable cell, there are two types of Ca2+ channels, L-type channels (Cav1.2) and SOC channels which are the majority; the rare is Cav1.2. A previous study found that Orai1-mediated Ca 2+ influx decreased endothelial nitric oxide synthase (eNOS) expression induced by tunicamycin, which attributes to endothelial dysfunction [ 21 ]. This is consistent with our finding that Orai1 and TRPC1 regulated Ca 2+ entry contribute to endothelial apoptosis [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

Role of store-operated Ca2+ entry in cardiovascular disease

Lu¹,

Zhang²,

Su³

et al. 2022

Cell Commun Signal

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Store-operated channels (SOCs) are highly selective Ca2+ channels that mediate Ca2+ influx in non-excitable and excitable (i.e., skeletal and cardiac muscle) cells. These channels are triggered by Ca2+ depletion of the endoplasmic reticulum and sarcoplasmic reticulum, independently of inositol 1,4,5-trisphosphate (InsP3), which is involved in cell growth, differentiation, and gene transcription. When the Ca2+ store is depleted, stromal interaction molecule1 (STIM1) as Ca2+ sensor redistributes into discrete puncta near the plasma membrane and activates the protein Ca2+ release activated Ca2+ channel protein 1 (Orai1). Accumulating evidence suggests that SOC is associated with several physiological roles in endothelial dysfunction and vascular smooth muscle proliferation that contribute to the progression of cardiovascular disease. This review mainly elaborates on the contribution of SOC in the vasculature (endothelial cells and vascular smooth muscle cells). We will further retrospect the literature implicating a critical role for these proteins in cardiovascular disease. Graphical Abstract

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Section: Introductionmentioning

confidence: 99%

Role of store-operated Ca2+ entry in cardiovascular disease

Lu¹,

Zhang²,

Su³

et al. 2022

Cell Commun Signal

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“…Furthermore, high glucose induced the up-regulation of Ora1-3 proteins and enhanced SOCE activity in human coronary artery endothelial cells (HCAECs), thereby inducing endothelial hyperpermeability and hyperproliferation [ 180 ]. In agreement with these observations, the genetic silencing of STIM1 and Orai1 alleviated the increase in permeability induced by the pro-inflammatory mediator, High-Mobility Group Box 1 protein (HMGB1), in Ea.hy926 monolayers [ 181 ], whereas a selective siOrai1 alleviated tunicamycin-induced ER stress and unfolded protein response, which are a feature of atherosclerosis, were shown to be alleviated by a selective siOrai1 in HUVECs [ 182 ]. Thus, the mechanisms by which chronic inflammation or hyperglycaemia lead to atherosclerosis involve an increase in endothelial permeability and proliferation that depend on STIM1 and Orai1 ( Table 4 ) [ 183 ].…”

Section: The Endothelial I Crac Is Mediated By Sti...mentioning

confidence: 80%

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

Moccia

Brunetti

Perna

et al. 2023

IJMS

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

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“…In a study by Wen et al [ 40 ], they stimulated mammary epithelial cell line, MCF-7 cells, for 24 h with tunicamycin at four different concentrations (0, 0.1, 0.5, and 1 µg/mL), finding that tunicamycin concentrations of 0.5 and 1 µg/mL significantly increased the expression of GRP-78 and caused ER stress, and they finally selected 1 µg/mL tunicamycin to build ER stress model for their follow-up experiment. Similarly, Yang et al [ 41 ]. treated human umbilical vein endothelial cells for 24 h with tunicamycin at five different concentrations (0, 0.25, 0.5, 1, and 2 µg/mL), finding that all concentrations (except concentration = 0) of tunicamycin significantly increased the expression of GRP-78 and caused ER stress, and the expression of GRP-78 was not a significant difference among the three concentrations (0.5, 1, and 2 µg/mL).…”

Section: Discussionmentioning

confidence: 94%

Resolvin D1 alleviates apoptosis triggered by endoplasmic reticulum stress in IPEC-J2 cells

Zhu,

Liu,

Wang

et al. 2024

BMC Vet Res

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Background Resolvin D1 (RvD1), a specialized pro-resolving lipid mediator (SPM), is derived from docosahexaenoic acid (DHA). It plays a key role in actively resolving inflammatory responses, which further reduces small intestinal damage. However, its regulation of the apoptosis triggered by endoplasmic reticulum (ER) stress in intestinal epithelial cells is still poorly understood. The intestinal porcine epithelial cells (IPEC-J2) were stimulated with tunicamycin to screen an optimal stimulation time and concentration to establish an ER stress model. Meanwhile, RvD1 (0, 1, 10, 20, and 50 nM) cytotoxicity and its impact on cell viability and the effective concentration for reducing ER stress and apoptosis were determined. Finally, the effects of RvD1 on ER stress and associated apoptosis were furtherly explored by flow cytometry analysis, AO/EB staining, RT-qPCR, and western blotting. Results The ER stress model of IPEC-J2 cells was successfully built by stimulating the cells with 1 µg/mL tunicamycin for 9 h. Certainly, the increased apoptosis and cell viability inhibition also appeared under the ER stress condition. RvD1 had no cytotoxicity, and its concentration of 1 nM significantly decreased cell viability inhibition (p= 0.0154) and the total apoptosis rate of the cells from 14.13 to 10.00% (p= 0.0000). RvD1 at the concentration of 1 nM also significantly reduced the expression of glucose-regulated protein 78 (GRP-78, an ER stress marker gene) (p= 0.0000) and pro-apoptotic gene Caspase-3 (p= 0.0368) and promoted the expression of B cell lymphoma 2 (Bcl-2, an anti-apoptotic gene)(p= 0.0008). Conclusions Collectively, the results shed light on the potential of RvD1 for alleviating apoptosis triggered by ER stress, which may indicate an essential role of RvD1 in maintaining intestinal health and homeostasis.

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Involvement of Orai1 in tunicamycin-induced endothelial dysfunction

Cited by 6 publications

References 28 publications

Role of store-operated Ca2+ entry in cardiovascular disease

Role of store-operated Ca2+ entry in cardiovascular disease

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

Resolvin D1 alleviates apoptosis triggered by endoplasmic reticulum stress in IPEC-J2 cells

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