Regulation of Orai1/STIM1 by the kinases SGK1 and AMPK

Läng, Florian; Eylenstein, Anja; Shumilina, Ekaterina

doi:10.1016/j.ceca.2012.05.005

Cited by 66 publications

(56 citation statements)

References 174 publications

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“…The effect of higher aldosterone concentrations is, however, blunted by the glucocorticoid antagonist mifepristone, an observation pointing to effects of glucocorticoid receptors. Noteworthy, both, mineralocorticoid and glucocorticoid receptors upregulate the serum & glucocorticoid inducible kinase (SGK1) which has been shown to upregulate Orai1 dependent Ca 2+ entry by activating NFκB [37]. Along those lines, pharmacological SGK1 inhibition reversed the effect of aldosterone on FGF23 expression.…”

Section: Discussionmentioning

confidence: 99%

NFκB-sensitive Orai1 expression in the regulation of FGF23 release

et al. 2015

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Fibroblast growth factor (FGF23) plasma levels are elevated in cardiac and renal failure and correlate with poor clinical prognosis of those disorders. Both disorders are associated with inflammation and activation of the inflammatory transcription factor NFB. An excessive FGF23 level is further observed in Klotho-deficient mice. The present study explored a putative sensitivity of FGF23 expression to transcription factor NFB, which is known to upregulate Orai1, the Ca(2+) channel accomplishing storeoperated Ca(2+) entry (SOCE). In osteoblastic cells (UMR106) and immortalized primary periosteal (IPO) cells, protein abundance was determined by Western blotting, and in UMR106 cells, transcript levels were quantified by RT-PCR, cytosolic Ca(2+) activity utilizing Fura-2-fluorescence, and SOCE from Ca(2+) entry following store depletion by thapsigargin. As a result, UMR106 and IPO cells expressed Ca(2+) channel Orai1. SOCE was lowered by NFB inhibitor wogonin as well as by Orai1 inhibitors 2-APB and YM58483. UMR106 cell Fgf23 transcripts were increased by stimulation of SOCE and Ca(2+) ionophore ionomycin and decreased by Orai inhibitors 2-APB, YM58483 and SKF96365, by Orai1 silencing, as well as by NFB inhibitors wogonin, withaferin A, and CAS 545380-34-5. In conclusion, Fgf23 expression is upregulated by stimulation of NFB-sensitive, store-operated Ca(2+) entry. KEY MES-SAGES Osteoblast UMR106 and IPO cells express Ca(2+) channel Orai1. Osteoblast store-operated Ca(2+) entry is accomplished by NFB-sensitive Orai1. Osteoblast Fgf23 transcription is upregulated by increase in the cytosolic Ca(2+) activity.

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Section: Discussionmentioning

confidence: 99%

NFκB-sensitive Orai1 expression in the regulation of FGF23 release

et al. 2015

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“…The effect of higher aldosterone concentrations is, however, blunted by the glucocorticoid antagonist mifepristone, an observation pointing also to an involvement of glucocorticoid receptors. Noteworthy, both, mineralocorticoid and glucocorticoid receptors upregulate the serum & glucocorticoid inducible kinase (SGK1) which has been shown to induce Orai1-dependent Ca 2+ entry by activating [27]. Along those lines, pharmacological SGK1 inhibition reversed the effect of aldosterone on Fgf23 expression.…”

Section: Discussionmentioning

confidence: 99%

Up-regulation of FGF23 release by aldosterone

Zhang

Umbach

Chen

et al. 2016

Biochemical and Biophysical Research Communications

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The fibroblast growth factor (FGF23) plasma level is high in cardiac and renal failure and is associated with poor clinical prognosis of these disorders. Both diseases are paralleled by hyperaldosteronism. Excessive FGF23 levels and hyperaldosteronism are further observed in Klotho-deficient mice. The present study explored a putative aldosterone sensitivity of Fgf23 transcription and secretion the putative involvement of the aldosterone sensitive serum glucocorticoid inducible kinase SGK1, SGK1 sensitive transcription factor NFB and store operated Ca(2+) entry (SOCE). Serum FGF23 levels were determined by ELISA in mice following sham treatment or exposure to deoxycorticosterone acetate (DOCA) or salt depletion. In osteoblastic UMR106 cells transcript levels were quantified by qRT-PCR, cytosolic Ca(2+) concentration utilizing Fura-2-fluorescence, and SOCE from Ca(2+) entry following store depletion by thapsigargin. As a result, DOCA treatment and salt depletion of mice elevated the serum C-terminal FGF23 concentration. In UMR106 cells aldosterone enhanced and spironolactone decreased SOCE. Aldosterone further increased Fgf23 transcript levels in UMR106 cells, an effect reversed by mineralocorticoid receptor blockers spironolactone and eplerenone, SGK1 inhibitor EMD638683, NFB-inhibitor withaferin A, and Ca(2+) channel blocker YM58483. In conclusion, Fgf23 expression is up-regulated by aldosterone, an effect sensitive to SGK1, NFB and store-operated Ca(2+) entry. AbstractThe fibroblast growth factor (FGF23) plasma level is high in cardiac and renal failure and is associated with poor clinical prognosis of these disorders. Both diseases are paralleled with hyperaldosteronism. Excessive FGF23 levels and hyperaldosteronism are further observed in Klotho-deficient mice. The present study explored a putative aldosterone sensitivity of Fgf23 transcription and secretion and the putative involvement of the aldosterone sensitive serum & glucocorticoid inducibe kinase SGK1 and SGK1 sensitive and store operated Ca 2+ entry (SOCE). Serum FGF23 levels were determined by ELISA in mice following sham treatment or exposure to deoxycorticosterone acetate (DOCA) or salt depletion. In osteoblastic UMR106 cells transcript levels were quantified by qRT-PCR, cytosolic Ca 2+ concentration utilizing Fura-2-fluorescence, and SOCE from Ca 2+ entry following store depletion by thapsigargin. As a result, DOCA treatment and salt depletion of mice elevated the serum C-terminal FGF23 concentration. In UMR106 cells aldosterone enhanced and spironolactone decreased SOCE. Aldosterone further increased Fgf23 transcript levels in UMR106 cells, an effect reversed by mineralocorticoid receptor blockers spironolactone and eplerenone, SGK1 inhibitor EMD638683, -inhibitor withaferin A, and Ca 2+ channel blocker YM58483. In conclusion, Fgf23 expression is up-regulated by aldosterone, an effect sensitive to SGK1, and store-operated Ca 2+ entry.

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“…This could be regulated either through changes in the phosphorylation of STIM1 and/or its interacting proteins, as well as via conformational changes in STIM1 resulting from refilling of ER/SR Ca 2ϩ stores. Interestingly, the STIM1/Orai1 complex appears to be regulated by the kinases SGK-1 and AMPK, which may reduce unnecessary SOCE when energy reserves are low (48). In addition, the ER membrane protein SARAF, also known as transmembrane protein 66, has been shown to associate with STIM1 in the ER, acting as a regulator of SOCE inactivation to prevent excess Ca 2ϩ refilling of the stores (81).…”

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confidence: 99%

STIM1/Orai1-mediated SOCE: current perspectives and potential roles in cardiac function and pathology

Collins

Zhu-Mauldin

Marchase

et al. 2013

American Journal of Physiology-Heart and Circulatory Physiology

110

102

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Collins HE, Zhu-Mauldin X, Marchase RB, Chatham JC. STIM1/Orai1-mediated SOCE: current perspectives and potential roles in cardiac function and pathology. Am J Physiol Heart Circ Physiol 305: H446 -H458, 2013. First published June 21, 2013 doi:10.1152/ajpheart.00104.2013.-Store-operated Ca 2ϩ entry (SOCE) is critical for Ca 2ϩ signaling in nonexcitable cells; however, its role in the regulation of cardiomyocyte Ca 2ϩ homeostasis has only recently been investigated. The increased understanding of the role of stromal interaction molecule 1 (STIM1) in regulating SOCE combined with recent studies demonstrating the presence of STIM1 in cardiomyocytes provides support that this pathway co-exists in the heart with the more widely recognized Ca 2ϩ handling pathways associated with excitation-contraction coupling. There is now substantial evidence that STIM1-mediated SOCE plays a key role in mediating cardiomyocyte hypertrophy, both in vitro and in vivo, and there is growing support for the contribution of SOCE to Ca 2ϩ overload associated with ischemia/reperfusion injury. Here, we provide an overview of our current understanding of the molecular regulation of SOCE and discuss the evidence supporting the role of STIM1/Orai1-mediated SOCE in regulating cardiomyocyte function.store-operated Ca 2ϩ entry; stromal interaction molecule 1; orai1; cardiomyocytes STORE-OPERATED CA 2ϩ ENTRY (SOCE), also known as capacitative calcium entry (CCE), is the major mechanism of Ca 2ϩ entry in nearly all nonexcitable cells (97, 99). In addition, it is increasingly recognized to co-exist with voltage-gated Ca 2ϩ channels in excitable cells, including neurons, skeletal muscle cells, and cardiomyocytes (1,38,45,83,121). In response to inositol 1,4,5-triphosphate (IP 3 )-(43) or ryanodine receptor (RyR)-mediated (3) Ca 2ϩ release from ER/SR stores, SOCE facilitates the influx of Ca 2ϩ from the extracellular space, resulting in a sustained increase in cytosolic Ca 2ϩ levels. Thus, although one of the roles of SOCE is to rapidly refill the depleted ER/SR stores, the subsequent sustained increase in cytosolic Ca 2ϩ also regulates numerous gene transcription pathways (33,50,151). Indeed, aberrant SOCE has been observed in a growing number of diseases including severe combined immunodeficiency, acute pancreatitis, and Alzheimer's disease (86).The integration of SOCE into well-established models of Ca 2ϩ homeostasis was hampered for many years by the lack of specific molecular mediators; even as recently as 2004 there was considerable controversy as to the specific mechanisms regulating SOCE (90, 113). However, in 2005, stromal interaction molecule 1 (STIM1) was found to localize to the ER/SR membrane and shown to function as a primary mediator of SOCE (54, 102). The putative physiological and pathophysiological roles of SOCE and STIM1 that have been identified to date are summarized in Table 1. A number of studies have recently reported the presence of STIM1 in adult cardiomyocytes (37,59,153), and consistent with earlier evidence supporting a rol...

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Regulation of Orai1/STIM1 by the kinases SGK1 and AMPK

Cited by 66 publications

References 174 publications

NFκB-sensitive Orai1 expression in the regulation of FGF23 release

NFκB-sensitive Orai1 expression in the regulation of FGF23 release

Up-regulation of FGF23 release by aldosterone

STIM1/Orai1-mediated SOCE: current perspectives and potential roles in cardiac function and pathology

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