Down-Regulation of Store-Operated Ca2+ Entry and Na+ Ca2+ Exchange in MCF-7 Breast Cancer Cells by Pharmacological JAK3 Inhibition

Yan, Jing; Zhang, Bingbing; Hosseinzadeh, Zohreh; Läng, Florian

doi:10.1159/000443104

Cited by 11 publications

(9 citation statements)

References 81 publications

(79 reference statements)

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“…The pipette solution contained (in mM/l): 35 NaCl, 120 CsCl, 10 HEPES/CsOH, 10 ethylene glycol tetraacetic acid (EGTA) and 0.04 inositol 1, 4,5-triphosphate (Ins(1, 4,5)P 3, Enzo Life Sciences), pH 7.4. The external solution contained (in mM/l) 140 NaCl, 5 KCL, 10 CaCl 2 , 20 glucose, 10 HEPES/NaOH, pH 7.4 [46].…”

Section: Patch Clampmentioning

confidence: 99%

Inhibition of Lithium Sensitive Orai1/ STIM1 Expression and Store Operated Ca2+ Entry in Chorea-Acanthocytosis Neurons by NF-κB Inhibitor Wogonin

Sukkar¹,

Hauser²,

Pelzl³

et al. 2018

Cell Physiol Biochem

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Background/Aims: The neurodegenerative disease Chorea-Acanthocytosis (ChAc) is caused by loss-of-function-mutations of the chorein-encoding gene VPS13A. In ChAc neurons transcript levels and protein abundance of Ca²⁺ release activated channel moiety (CRAC) Orai1 as well as its regulator STIM1/2 are decreased, resulting in blunted store operated Ca²⁺-entry (SOCE) and enhanced suicidal cell death. SOCE is up-regulated and cell death decreased by lithium. The effects of lithium are paralleled by upregulation of serum & glucocorticoid inducible kinase SGK1 and abrogated by pharmacological SGK1 inhibition. In other cell types SGK1 has been shown to be partially effective by upregulation of NFκB, a transcription factor stimulating the expression of Orai1 and STIM. The present study explored whether pharmacological inhibition of NFκB interferes with Orai1/STIM1/2 expression and SOCE and their upregulation by lithium in ChAc neurons. Methods: Cortical neurons were differentiated from induced pluripotent stem cells generated from fibroblasts of ChAc patients and healthy volunteers. Orai1 and STIM1 transcript levels and protein abundance were estimated from qRT-PCR and Western blotting, respectively, cytosolic Ca²⁺-activity ([Ca²⁺]_i) from Fura-2-fluorescence, SOCE from increase of [Ca²⁺]_i following Ca²⁺ re-addition after Ca²⁺-store depletion with sarco-endoplasmatic Ca²⁺-ATPase inhibitor thapsigargin (1µM), as well as CRAC current utilizing whole cell patch clamp recording. Results: Orai1 and STIM1 transcript levels and protein abundance as well as SOCE and CRAC current were significantly enhanced by lithium treatment (2 mM, 24 hours). These effects were reversed by NFκB inhibitor wogonin (50 µM). Conclusion: The stimulation of expression and function of Orai1/STIM1/2 by lithium in ChAc neurons are disrupted by pharmacological NFκB inhibition.

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Section: Patch Clampmentioning

confidence: 99%

Inhibition of Lithium Sensitive Orai1/ STIM1 Expression and Store Operated Ca2+ Entry in Chorea-Acanthocytosis Neurons by NF-κB Inhibitor Wogonin

Sukkar¹,

Hauser²,

Pelzl³

et al. 2018

Cell Physiol Biochem

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“…Intracellular Ca 2+ concentration is regulated by a variety of systems and mechanisms such as Ca 2+ release from intracellular stores with subsequent stimulation of store operated calcium entry(SOCE) [5,6] and Na + /Ca 2+ exchangers(NCX) [7][8][9][10]. NCX is a transporter that can move sodium across the membrane in exchange for calcium [11][12][13]. The carrier extrudes Ca 2+ at high intracellular Ca 2+ concentration and at hyper-polarized cell membrane potential, whereas at high intracellular Na + concentration and depolarized cell membrane the carrier is reversed thus mediating Ca 2+ entry [14,15].…”

Section: Dysregulation Of Intracellular Camentioning

confidence: 99%

“…NCX is a transporter that can move sodium across the membrane in exchange for calcium [11][12][13]. The carrier extrudes Ca 2+ at high intracellular Ca 2+ concentration and at hyper-polarized cell membrane potential, whereas at high intracellular Na + concentration and depolarized cell membrane the carrier is reversed thus mediating Ca 2+ entry [14,15]. Given the ubiquitous involvement of Ca 2+ signaling in AD, NCX may play a pivotal role in AD pathogenesis.…”

Section: Dysregulation Of Intracellular Camentioning

confidence: 99%

“…Upon binding to its receptor [24], leptin leads to the activation of several intracellular signaling pathways [25] including JAK-STAT [26,27]. JAK signaling is a candidate involved in the regulation of Ca 2+ signalling [14,28,29]. It is reported that pharmacological inhibition of JAK3 decreases SOCE and NCX in MCF-7 Breast Cancer Cells [12].…”

Section: Dysregulation Of Intracellular Camentioning

confidence: 99%

“…JAK signaling is a candidate involved in the regulation of Ca 2+ signalling [14,28,29]. It is reported that pharmacological inhibition of JAK3 decreases SOCE and NCX in MCF-7 Breast Cancer Cells [12]. Moreover, Leptin downregulates epithelial Na + channel(ENaC) activity [30], which in turn causes high extracellular Na + concentration.…”

Section: Dysregulation Of Intracellular Camentioning

confidence: 99%

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Effects of Leptin on Na+/Ca2+ Exchanger in PC12 Cells

Zhang

Sun

et al. 2016

Cell Physiol Biochem

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Background/Aims: Alzheimer's disease (AD) is known to be related to alterations in neuronal intracellular calcium activity ([Ca²⁺]_i). The present study revealed the distinct role of leptin in Na⁺/Ca²⁺-exchanger activity. Methods: [Ca²⁺]_i was determined utilizing Fura-2 fluorescence. The activity of NCX was measured by removal of extracellular Na⁺ in the presence of external Ca²⁺. Na⁺/Ca²⁺-exchanger activity was further quantified from whole cell currents following removal of extracellular Na⁺. Na⁺/Ca²⁺-exchanger isoform NCX1 transcript levels and protein abundance were quantified by RT-PCR and Western blotting, respectively. Results: Exposure of PC12 cells to 30 µM amyloid (Aβ₄₂) increased [Ca²⁺]_i, an effect significantly blunted by 6 hours incubation with leptin before Aβ₄₂ treatment. Moreover, leptin treatment significantly increased Na⁺/Ca²⁺-exchanger mediated Ca+ transport and current, NCX1 transcript level as well as NCX1 membrane protein abundance. Conclusion: We show that leptin blunts Aβ₄₂-evoked [Ca²⁺]_i increase by increasing expression and activity of Na⁺/Ca²⁺-exchanger NCX1.

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Inhibition of altered Orai1 channels in Müller cells protects photoreceptors in retinal degeneration

Sukkar,

Oktay,

Sahaboglu

et al. 2023

Glia

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The expressions of ion channels by Müller glial cells (MGCs) may change in response to various retinal pathophysiological conditions. There remains a gap in our understanding of MGCs' responses to photoreceptor degeneration towards finding therapies. The study explores how an inhibition of store‐operated Ca2+ entry (SOCE) and its major component, Orai1 channel, in MGCs protects photoreceptors from degeneration. The study revealed increased Orai1 expression in the MGCs of retinal degeneration 10 (rd10) mice. Enhanced expression of oxidative stress markers was confirmed as a crucial pathological mechanism in rd10 retina. Inducing oxidative stress in rat MGCs resulted in increasing SOCE and Ca2+ release‐activated Ca2+ (CRAC) currents. SOCE inhibition by 2‐Aminoethoxydiphenyl borate (2‐APB) protected photoreceptors in degenerated retinas. Finally, molecular simulations proved the structural and dynamical features of 2‐APB to the target structure Orai1. Our results provide new insights into the physiology of MGCs regarding retinal degeneration and shed a light on SOCE and Orai1 as new therapeutic targets.

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Down-Regulation of Store-Operated Ca2+ Entry and Na+ Ca2+ Exchange in MCF-7 Breast Cancer Cells by Pharmacological JAK3 Inhibition

Abstract: Background

Cited by 11 publications

References 81 publications

Inhibition of Lithium Sensitive Orai1/ STIM1 Expression and Store Operated Ca2+ Entry in Chorea-Acanthocytosis Neurons by NF-κB Inhibitor Wogonin

Inhibition of Lithium Sensitive Orai1/ STIM1 Expression and Store Operated Ca2+ Entry in Chorea-Acanthocytosis Neurons by NF-κB Inhibitor Wogonin

Effects of Leptin on Na+/Ca2+ Exchanger in PC12 Cells

Inhibition of altered Orai1 channels in Müller cells protects photoreceptors in retinal degeneration

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