Glucocorticoid-mediated co-regulation of RCAN1-1, E4BP4 and BIM in human leukemia cells susceptible to apoptosis

Saenz, G. Jonatan; Hovanessian, Rebeka; Gisis, Andrew D.; Medh, Rheem D.

doi:10.1016/j.bbrc.2015.06.106

Cited by 9 publications

(12 citation statements)

References 33 publications

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“…While different inducers of Ca 2+ selectively upregulate Rcan1-4, few stimuli have been described as modulators of Rcan1-1 expression. A role for apoptosis is attributed to Rcan1-1 in response to glucocorticoids, and relevant studies have linked Rcan1-1 to Huntington disease ( 28 , 29 ). Rcan1-4 is upregulated by increases in Ca 2 or in response to a variety of signals, including cytokines, hormones, hydrogen peroxide, and stress ( 30 ).…”

Section: Introductionmentioning

confidence: 99%

Endothelial Regulator of Calcineurin 1 Promotes Barrier Integrity and Modulates Histamine-Induced Barrier Dysfunction in Anaphylaxis

et al. 2017

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Anaphylaxis, the most serious and life-threatening allergic reaction, produces the release of inflammatory mediators by mast cells and basophils. Regulator of calcineurin 1 (Rcan1) is a negative regulator of mast-cell degranulation. The action of mediators leads to vasodilation and an increase in vascular permeability, causing great loss of intravascular volume in a short time. Nevertheless, the molecular basis remains unexplored on the vascular level. We investigated Rcan1 expression induced by histamine, platelet-activating factor (PAF), and epinephrine in primary human vein (HV)-/artery (HA)-derived endothelial cells (ECs) and human dermal microvascular ECs (HMVEC-D). Vascular permeability was analyzed in vitro in human ECs with forced Rcan1 expression using Transwell migration assays and in vivo using Rcan1 knockout mice. Histamine, but neither PAF nor epinephrine, induced Rcan1-4 mRNA and protein expression in primary HV-ECs, HA-ECs, and HMVEC-D through histamine receptor 1 (H1R). These effects were prevented by pharmacological inhibition of calcineurin with cyclosporine A. Moreover, intravenous histamine administration increased Rcan1 expression in lung tissues of mice undergoing experimental anaphylaxis. Functional in vitro assays showed that overexpression of Rcan1 promotes barrier integrity, suggesting a role played by this molecule in vascular permeability. Consistent with these findings, in vivo models of subcutaneous and intravenous histamine-mediated fluid extravasation showed increased response in skin, aorta, and lungs of Rcan1-deficient mice compared with wild-type animals. These findings reveal that endothelial Rcan1 is synthesized in response to histamine through a calcineurin-sensitive pathway and may reduce barrier breakdown, thus contributing to the strengthening of the endothelium and resistance to anaphylaxis. These new insights underscore its potential role as a regulator of sensitivity to anaphylaxis in humans.

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Section: Introductionmentioning

confidence: 99%

Endothelial Regulator of Calcineurin 1 Promotes Barrier Integrity and Modulates Histamine-Induced Barrier Dysfunction in Anaphylaxis

et al. 2017

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“…Two genes inhibitory to CaN are induced by Dex in both apoptosis-sensitive clones but not in the resistant clone. These are CABIN1 (Esau, Boes, Youn et al, 2001) and Calcipressin 1/RCAN1/DSCR1/Adapt78/RCN1 (Harris, Ermak and Davies 2005, Cook, Hejna, Magnuson et al 2005, Chan, Greenan, McKeon et al 2005, Nagao, Iwai and Miyashita 2012, Saenz, Hovanessian, Gisis et al, 2015). Calcipressin 1/DSCR1 is strongly induced in both Dex-sensitive clones but only weakly, if at all, in CEM C1-15 cells (Table 3).…”

Section: Resultsmentioning

confidence: 99%

Sequential gene regulatory events leading to glucocorticoid-evoked apoptosis of CEM human leukemic cells:interactions of MAPK, MYC and glucocorticoid pathways

Webb

Miller

Howard

et al. 2018

Molecular and Cellular Endocrinology

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Gene expression responses to glucocorticoid (GC) in the hours preceding onset of apoptosis were compared in three clones of human acute lymphoblastic leukemia CEM cells. Between 2 and 20h, all three clones showed increasing numbers of responding genes. Each clone had many unique responses, but the two responsive clones showed a group of responding genes in common, different from the resistant clone. MYC levels and the balance of activities between the three major groups of MAPKs are known important regulators of glucocorticoid-driven apoptosis in several lymphoid cell systems. Common to the two sensitive clones were changed transcript levels from genes that decrease amounts or activity of anti-apoptotic ERK/MAPK1 and JNK2/MAPK9, or of genes that increase activity of pro-apoptotic p38/MAPK14. Down-regulation of MYC and several MYC-regulated genes relevant to MAPKs also occurred in both sensitive clones. Transcriptomine comparisons revealed probable NOTCH-GC crosstalk in these cells.

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“…Here, we primarily focused on the inhibition of NF-κB activity in tumor cells. And recent study has verified the RCAN1 can suppress cancer growth [ 4 , 7 , 26 ] by inhibiting NF-κB signaling pathway. In our study, we verified NF-κB signaling pathway was activated in glioma tissues.…”

Section: Discussionmentioning

confidence: 99%

The regulator of calcineurin 1 (RCAN1) inhibits nuclear factor kappaB signaling pathway and suppresses human malignant glioma cells growth

Chen

Wang

et al. 2017

Oncotarget

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Nuclear factor-kappaB (NF-κB) has a vital role in cell survival and inhibition of NF-κB had proven to be an efficient therapeutic pathway for various cancers though little is known about the underlying mechanism. Previously we identified regulator of calcineurin 1 (RCAN1) as an endogenous inhibitor of NF-κB signaling pathway in lymphoma. In the present study, we have solid data to show that RCAN1 can inhibit the nuclear translocation of NF-κB protein then affect the activity of NF-κB signaling pathway in glioma cells. Overexpression of RCAN1 markedly reduced glioma cells viability. We further found that the suppressing glioma cell growth was closely related to the pro-apoptosis effect, not by inhibiting proliferation by the arrest of cell cycle. Our study implicated a novel therapeutic approach for glioma by RCAN1 through inhibition of NF-κB signaling.

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Glucocorticoid-mediated co-regulation of RCAN1-1, E4BP4 and BIM in human leukemia cells susceptible to apoptosis

Cited by 9 publications

References 33 publications

Endothelial Regulator of Calcineurin 1 Promotes Barrier Integrity and Modulates Histamine-Induced Barrier Dysfunction in Anaphylaxis

Endothelial Regulator of Calcineurin 1 Promotes Barrier Integrity and Modulates Histamine-Induced Barrier Dysfunction in Anaphylaxis

Sequential gene regulatory events leading to glucocorticoid-evoked apoptosis of CEM human leukemic cells:interactions of MAPK, MYC and glucocorticoid pathways

The regulator of calcineurin 1 (RCAN1) inhibits nuclear factor kappaB signaling pathway and suppresses human malignant glioma cells growth

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