The negative effect of dexamethasone on calcium-processing gene expressions is associated with a glucocorticoid-induced calcium-absorbing disorder

Kim, Man-Hee; Lee, Geun‐Shik; Jung, Eui‐Man; Choi, Kyung‐Chul; Jeung, Eui‐Bae

doi:10.1016/j.lfs.2009.05.013

Cited by 31 publications

(23 citation statements)

References 49 publications

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“…Recently, Sun and Zemel (17) reported the increase of Vdr mRNA with Dex in 3T3-L1 adipocyte model. Similarly, Dex increases expression of renal VDR in mice (22). Our study shows de novo transcription of Vdr by Dex that results in increased VDR protein, increases sensitivity to calcitriol, and potentiates VDR-mediated transcription of VDR and many VDR target genes including p21, p27, cyclin D1, and calbindin D9K (Fig.…”

Section: Discussionsupporting

confidence: 56%

“…Regulation of Vdr expression by Dex has been recently reported in the intestine where long term Dex treatment leads to a reduction in expression of Vdr (22). Those findings may correlate with the role of Dex preventing calcitriol hypercalcemic effects.…”

Section: Discussionmentioning

confidence: 62%

“…In our current study, we found that Dex increases VDR by increasing transcription of Vdr gene in a GR-dependent manner. Increased VDR levels with Dex have also been shown in adipocytes and kidney and endothelial cells derived from tumors (6,17,22). In support of cross-talk between VDR and GR signaling axes, it was reported that calcitriol positively affects glucocorticoid production in human adipocytes through increasing 11␤-hydroxysteroid dehydrogenase type 1, which promotes the conversion of the glucocorticoid precursor, cortisone, to cortisol (51).…”

Section: Discussionmentioning

confidence: 92%

“…In addition, a number of transcription factors have been found to regulate VDR expression, including p63, p53, and Sp1 (30 -32). Up-regulation of VDR with Dex treatment has been reported in several models (6,16,17,22). We cloned several fragments upstream of the Vdr transcription start site and within introns into a luciferase reporter vector to find active GREs.…”

Section: Discussionmentioning

confidence: 99%

“…Glucocorticoids, such as dexamethasone, have anti-calcemic effects that decrease intestinal calcium absorption and increased urinary excretion of calcium (22)(23)(24)(25) (22). Because of the anti-calcemic effects of Dex, our laboratory has studied the effects of calcitriol and Dex combination to improve calcitriol therapy and reduce the hypercalcemic effects of calcitriol (3).…”

mentioning

confidence: 99%

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Dexamethasone Enhances 1α,25-Dihydroxyvitamin D3 Effects by Increasing Vitamin D Receptor Transcription

Hidalgo

Deeb

Pike

et al. 2011

Journal of Biological Chemistry

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Background: Dexamethasone increases vitamin D receptor and anti-proliferative effects of calcitriol. Result: Glucocorticoid receptor binds to response elements within regulatory region of Vdr gene to drive its transcription. Conclusion: Dexamethasone induces de novo transcription of the vitamin D receptor in a glucocorticoid receptor-dependent manner. Significance: A proposed mechanism by which glucocorticoids increase vitamin D receptor and calcitriol activities.

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Section: Discussionsupporting

confidence: 56%

Section: Discussionmentioning

confidence: 62%

Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Dexamethasone Enhances 1α,25-Dihydroxyvitamin D3 Effects by Increasing Vitamin D Receptor Transcription

Hidalgo

Deeb

Pike

et al. 2011

Journal of Biological Chemistry

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TRPV5: A Ca2+ Channel for the Fine-Tuning of Ca2+ Reabsorption

Peng

2014

Handbook of Experimental Pharmacology

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TRPV5 is one of the two channels in the TRPV family that exhibit high selectivity to Ca(2+) ions. TRPV5 mediates Ca(2+) influx into cells as the first step to transport Ca(2+) across epithelia. The specialized distribution in the distal tubule of the kidney positions TRPV5 as a key player in Ca(2+) reabsorption. The responsiveness in expression and/or activity of TRPV5 to hormones such as 1,25-dihydroxyvitamin D3, parathyroid hormone, estrogen, and testosterone makes TRPV5 suitable for its role in the fine-tuning of Ca(2+) reabsorption. This role is further optimized by the modulation of TRPV5 trafficking and activity via its binding partners; co-expressed proteins; tubular factors such as calbindin-D28k, calmodulin, klotho, uromodulin, and plasmin; extracellular and intracellular factors such as proton, Mg(2+), Ca(2+), and phosphatidylinositol-4,5-bisphosphate; and fluid flow. These regulations allow TRPV5 to adjust its overall activity in response to the body's demand for Ca(2+) and to prevent kidney stone formation. A point mutation in mouse Trpv5 gene leads to hypercalciuria similar to Trpv5 knockout mice, suggesting a possible role of TRPV5 in hypercalciuric disorders in humans. In addition, the single nucleotide polymorphisms in Trpv5 gene prevalently present in African descents may contribute to the efficient renal Ca(2+) reabsorption among African descendants. TRPV5 represents a potential therapeutic target for disorders with altered Ca(2+) homeostasis.

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TRPV6 Channels

Fecher‐Trost

Weißgerber

Wissenbach

2014

Handbook of Experimental Pharmacology

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TRPV6 (former synonyms ECAC2, CaT1, CaT-like) displays several specific features which makes it unique among the members of the mammalian Trp gene family (1) TRPV6 (and its closest relative, TRPV5) are the only highly Ca(2+)-selective channels of the entire TRP superfamily (Peng et al. 1999; Wissenbach et al. 2001; Voets et al. 2004). (2) Translation of Trpv6 initiates at a non-AUG codon, at ACG, located upstream of the annotated AUG, which is not used for initiation (Fecher-Trost et al. 2013). The ACG codon is nevertheless decoded by methionine. Not only a very rare event in eukaryotic biology, the full-length TRPV6 protein existing in vivo comprises an amino terminus extended by 40 amino acid residues compared to the annotated truncated TRPV6 protein which has been used in most studies on TRPV6 channel activity so far. (In the following numbering occurs according to this full-length protein, with the numbers of the so far annotated truncated protein in brackets). (3) Only in humans a coupled polymorphism of Trpv6 exists causing three amino acid exchanges and resulting in an ancestral Trpv6 haplotype and a so-called derived Trpv6 haplotype (Wissenbach et al. 2001). The ancestral allele encodes the amino acid residues C197(157), M418(378) and M721(681) and the derived alleles R197(157), V418(378) and T721(681). The ancestral haplotype is found in all species, the derived Trpv6 haplotype has only been identified in humans, and its frequency increases with the distance to the African continent. Apparently the Trpv6 gene has been a strong target for selection in humans, and its derived variant is one of the few examples showing consistently differences to the orthologues genes of other primates (Akey et al. 2004, 2006; Stajich and Hahn 2005; Hughes et al. 2008). (4) The Trpv6 gene expression is significantly upregulated in several human malignancies including the most common cancers, prostate and breast cancer (Wissenbach et al. 2001; Zhuang et al. 2002; Fixemer et al. 2003; Bolanz et al. 2008). (5) Male mice lacking functional TRPV6 channels are hypo-/infertile making TRPV6 one of the very few channels essential for male fertility (Weissgerber et al. 2011, 2012).

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The negative effect of dexamethasone on calcium-processing gene expressions is associated with a glucocorticoid-induced calcium-absorbing disorder

Cited by 31 publications

References 49 publications

Dexamethasone Enhances 1α,25-Dihydroxyvitamin D3 Effects by Increasing Vitamin D Receptor Transcription

Dexamethasone Enhances 1α,25-Dihydroxyvitamin D3 Effects by Increasing Vitamin D Receptor Transcription

TRPV5: A Ca2+ Channel for the Fine-Tuning of Ca2+ Reabsorption

TRPV6 Channels

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