Effect of Thymoquinone on Cytosolic pH and Na&lt;sup&gt;+&lt;/sup&gt;/H&lt;sup&gt;+&lt;/sup&gt; Exchanger Activity in Mouse Dendritic Cells

Yang, Wenting; Bhandaru, Madhuri; Pasham, Venkanna; Bobbala, Diwakar; Zelenak, Christine; Jilani, Kashif; Rotte, Anand; Läng, Florian

doi:10.1159/000337583

Cited by 20 publications

(13 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For digital imaging of cytosolic pH (pH i ) , the cells were incubated in a HEPES-buffered Ringer solution containing 10 µM BCECF-AM (Molecular Probes, Leiden, Netherlands) for 15 min at 37°C [49]. 4-6 slides per group from three independent experiments were imaged and analysed.…”

Section: Methodsmentioning

confidence: 99%

Sgk1-Dependent Stimulation of Cardiac Na⁺/H⁺Exchanger Nhe1 by Dexamethasone

Voelkl

Pasham

Ahmed

et al. 2013

Cell Physiol Biochem

Self Cite

682

View full text Add to dashboard Cite

Background/Aims: The serum- and glucocorticoid-inducible kinase Sgk1 contributes to cardiac remodeling and development of heart failure, which is paralelled by Sgk1-dependent stimulation of the cardiac Na⁺/H⁺ exchanger Nhe1. Glucocorticoids are powerful stimulators of Sgk1 expression and influence cardiac remodeling. The present study thus explored whether the glucocorticoid receptor agonist dexamethasone influenced cardiac Sgk1 expression, as well as activity, expression and phosphorylation at Ser⁷⁰³ of the cardiac Na⁺/H⁺ exchanger Nhe1. Methods: Experiments were performed in HL-1 cardiomyocytes and gene targeted mice lacking functional Sgk1 (sgk1^-/-) and respective wild type mice (sgk1^+/+). Gene expression was determined by quantitative RT-PCR and Nhe1 phosphorylation was determined utilizing a specific antibody against a 14-3-3 binding motif at P-Ser⁷⁰³, which represents a putative phosphorylation site recognition motif for Sgk1 and is involved in Nhe1 activation. Cytosolic pH (pH_i) was determined utilizing 2',7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein (BCECF) fluorescence and Nhe activity by the Na⁺-dependent realkalinization after an ammonium pulse. Results: Treatment of HL-1 cardiomyocytes with dexamethasone was followed by a significant increase in Sgk1 mRNA expression, parallelled by increased Na⁺/H⁺ exchanger activity. Furthermore, dexamethasone significantly increased Nhe1 and Spp1 mRNA expression. The effects of dexamethasone were blunted by cotreatment of HL-1 cardiomyocytes with the Sgk1 inhibitor EMD638683. Cotreatment with Nhe1 inhibitor cariporide similarly prevented dexamethasone-stimulated Spp1 mRNA expression. In sgk1^+/+ mice, dexamethasone significantly increased cardiac Sgk1 mRNA levels. In sgk1^+/+ mice, but not in sgk1^-/- mice, dexamethasone significantly increased cardiac Nhe1 mRNA expression and Nhe1 phosphorylation at Ser⁷⁰³. Furthermore, cardiac Spp1, Ctgf, Nppa and Nppb mRNA levels were significantly increased in dexamethasone treated sgk1^+/+ mice, effects significantly blunted in sgk1^-/- mice. Conclusions: Sgk1 is critically involved in the phosphorylation and activation of the cardiac Na⁺/H⁺ exchanger Nhe1.

show abstract

Section: Methodsmentioning

confidence: 99%

Sgk1-Dependent Stimulation of Cardiac Na⁺/H⁺Exchanger Nhe1 by Dexamethasone

Voelkl

Pasham

Ahmed

et al. 2013

Cell Physiol Biochem

Self Cite

682

View full text Add to dashboard Cite

show abstract

“…3). DCs are antigen-presenting cells contributing to both innate and adaptive immunity and thus playing a decisive role in the regulation of the immune response [98,99,100,101,102,103,104,105,106,107]. GA treatment of DCs is followed by upregulation of several maturation markers, such as CD86 [108] CD54 [109] and CD40 [110,111].…”

Section: Extrarenal Effects Of Gamentioning

confidence: 99%

Renal and Extrarenal Effects of Gum Arabic (Acacia Senegal) - What Can be Learned from Animal Experiments?

Nasir

2013

Kidney Blood Press Res

1,741

View full text Add to dashboard Cite

Gum arabic (GA), a water-soluble dietary fiber rich in Ca²⁺, Mg²⁺ and K⁺, is used in Middle Eastern countries for the treatment of patients with chronic kidney disease. Recent animal experiments shed some light into mechanisms involved in the therapeutic action of GA. According to experiments in healthy mice, GA treatment increases creatinine clearance, enhances renal excretion of ADH, Mg²⁺ and Ca²⁺, decreases plasma phosphate concentration as well as urinary excretion of phosphate and Na⁺. In diabetic mice GA treatment increases urinary Ca²⁺ excretion, and decreases plasma phosphate concentration, plasma urea concentration, urinary flow rate, natriuresis, phosphaturia, glucosuria, proteinuria as well as blood pressure. Extrarenal effects of GA treatment in mice include decreased expression of intestinal Na⁺ coupled glucose carrier SGLT1 with subsequent delay of electrogenic intestinal glucose transport, glucose-induced hyperglycemia, hyperinsulinemia and body weight gain. GA treatment decreases colonic transcription of the angiogenetic factors angiogenin 1, angiogenin 3 and angiogenin 4, of CD38 antigen, aquaporin4, interleukin18, vav-3-oncogene, y⁺-amino acid-transporter, sulfatase1, ubiquitinD and chemokine ligand5. Moreover, GA treatment decreases angiogenin and ß-catenin protein expression. Accordingly, GA treatment counteracts the development of tumors following chemical cancerogenesis. In mouse dendritic cells, antigen-presenting cells linking innate and adaptive immunity, GA treatment modifies maturation and cytokine release. GA treatment further favourably influences the course of murine malaria. The effects of GA treatment on plasma phosphate concentration, blood pressure and proteinuria may prove beneficial in chronic renal failure and diabetic nephropathy. The effect of GA on intestinal glucose transport may be useful in the prophylaxis and treatment of obesity and diabetes, the effect of GA on angiogenin and ß-catenin expression could be exploited for the prophylaxis against colon carcinoma, the effects of GA on angiogenin expression and dendritic cells may be useful in the treatment of inflammatory disease and malaria.

show abstract

“…Dendritic cells (DCs) were cultured from bone marrow of 8-12 week old female and male mice [29]. Bone marrow derived cells were flushed out of the cavities from the femur and tibia with PBS.…”

Section: Methodsmentioning

confidence: 99%

Serum- and Glucocorticoid-Inducible Kinase 1 Sensitive NF-κB Signaling in Dendritic Cells

Schmid

Xuân

Zahir

et al. 2014

Cell Physiol Biochem

Self Cite

View full text Add to dashboard Cite

Background/Aims: Dendritic cells (DCs), antigen-presenting cells linking innate and adaptive immunity, are required for initiation of specific T cell-driven immune responses. Phosphoinositide-3-kinase (PI3K) suppresses proinflammatory cytokine production in DCs, which limits T helper (Th1) polarization. PI3K is in part effective by downregulation of transcription factor NF-κB. Downstream signaling elements of PI3K include serum- and glucocorticoid-inducible kinase 1 (SGK1) and its phosphorylation target N-myc downstream regulated gene 1 (NDRG1). The present study explored whether SGK1 and NDRG1 play a role in the regulation of NF-κB and DC-maturation. Methods: DCs were isolated from bone marrow (BMDCs) or spleen of mice lacking functional SGK1 (sgk1^-/-) and corresponding wild type mice (sgk1^+/+). Protein abundance was determined by Western blotting. Transcription was inhibited by siRNA. Abundance of maturation markers was quantified by flow cytometry. FITC-dextran uptake was determined to quantify phagocytosis. Results: NDRG1 was similarly expressed in sgk1^+/+ and sgk1^-/-BMDCs, but SGK1-dependent phosphorylation of NDRG-1 was decreased in sgk1^-/-BMDCs. Silencing of NDRG1 in sgk1^+/+BMDCs as compared to control empty vector-treated BMDCs enhanced nuclear abundance of NF-κB subunit p65. Moreover, the abundance of phosphorylated NF-κB inhibitor IκBa, of phosphorylated IκB kinase (IKKa/ß) and of nuclear p65 were significantly higher in sgk1^-/-BMDCs than in sgk1^+/+BMDCs. Expression of maturation markers, MHC II, and CD86, was significantly larger and phagocytic capacity was significantly lower in sgk1^-/- than in sgk1^+/+BMDCs. Expression of CD86 and MHCII was also significantly higher in DCs isolated from the spleen of sgk1^-/- mice than those from sgk1^+/+mice. Conclusion: SGK1 and NDRG1 participate in the regulation of NF-κB signaling in and maturation of DCs.

show abstract

Effect of Thymoquinone on Cytosolic pH and Na<sup>+</sup>/H<sup>+</sup> Exchanger Activity in Mouse Dendritic Cells

Cited by 20 publications

References 53 publications

Sgk1-Dependent Stimulation of Cardiac Na⁺/H⁺Exchanger Nhe1 by Dexamethasone

Sgk1-Dependent Stimulation of Cardiac Na⁺/H⁺Exchanger Nhe1 by Dexamethasone

Renal and Extrarenal Effects of Gum Arabic (Acacia Senegal) - What Can be Learned from Animal Experiments?

Serum- and Glucocorticoid-Inducible Kinase 1 Sensitive NF-κB Signaling in Dendritic Cells

Contact Info

Product

Resources

About

Effect of Thymoquinone on Cytosolic pH and Na<sup>+</sup>/H<sup>+</sup> Exchanger Activity in Mouse Dendritic Cells

Cited by 20 publications

References 53 publications

Sgk1-Dependent Stimulation of Cardiac Na+/H+Exchanger Nhe1 by Dexamethasone

Sgk1-Dependent Stimulation of Cardiac Na+/H+Exchanger Nhe1 by Dexamethasone

Renal and Extrarenal Effects of Gum Arabic (Acacia Senegal) - What Can be Learned from Animal Experiments?

Serum- and Glucocorticoid-Inducible Kinase 1 Sensitive NF-&#954;B Signaling in Dendritic Cells

Contact Info

Product

Resources

About

Sgk1-Dependent Stimulation of Cardiac Na⁺/H⁺Exchanger Nhe1 by Dexamethasone

Sgk1-Dependent Stimulation of Cardiac Na⁺/H⁺Exchanger Nhe1 by Dexamethasone

Serum- and Glucocorticoid-Inducible Kinase 1 Sensitive NF-κB Signaling in Dendritic Cells