Determinants of circulating 1,25-dihydroxyvitamin D3 levels: the role of renal synthesis and catabolism of vitamin D

Anderson, Paul; O’Loughlin, Peter; May, Brian K.; Morris, Howard A.

doi:10.1016/j.jsbmb.2004.03.089

Cited by 46 publications

(26 citation statements)

References 14 publications

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“…Several different cell types, including cancer cells, have been shown to express 1a-hydroxylase and are therefore able to produce and regulate 1,25(OH)2D concentrations at the level of the individual tissue/cell (1,21,22). Furthermore, serum 1,25(OH)2D concentrations are tightly regulated by the kidney, decrease with (23)(24)(25)(26). Two interventional trials have already examined the effect of vitamin D supplementation on total cancer incidence/mortality (27,28).…”

Section: Discussionmentioning

confidence: 99%

Low Serum Levels of 25-Hydroxyvitamin D Predict Fatal Cancer in Patients Referred to Coronary Angiography

Pilz

Dobnig

Winklhofer‐Roob

et al. 2008

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Section: Discussionmentioning

confidence: 99%

Low Serum Levels of 25-Hydroxyvitamin D Predict Fatal Cancer in Patients Referred to Coronary Angiography

Pilz

Dobnig

Winklhofer‐Roob

et al. 2008

Cancer Epidemiology, Biomarkers &Amp; Prevention

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“…1,25(OH) 2 D 3 , the most important gene regulator, enters the nucleus and regulates mRNA synthesis by binding to VDR. The principal physiological function of 1,25(OH) 2 D 3 is enhancing the absorption of calcium and phosphate from the intestinal tract, therefore positively regulating bone formation [9][10][11] . To date, several lines of epidemiological and experimental findings have supported the links of vitamin D with various conditions or diseases beyond bone health [3] , including muscle function [12,13] , autoimmune diseases [14] , cancer [15,16] , cardiovascular diseases (CVD) [17][18][19] , hypertension [20,21] , diabetes [22] , inflammatory diseases [23] , and all-cause mortality [24] , etc.…”

Section: General Roles Of Vitamin D In Physiological Conditions and Dmentioning

confidence: 99%

Role of vitamin D in immune responses and autoimmune diseases, with emphasis on its role in multiple sclerosis

Zhang

2010

Neurosci. Bull.

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“…SB inhibitors are pyridinyl immidazole compounds have been widely used in investigation of the biological function of p38 MAPK (30). These compounds are also well known for their ability to inhibit TGF␤ receptor activation (59 activation on target genes (60).…”

Section: Renal P38␣ Activation By [Camentioning

confidence: 99%

“…Equal loading was checked by re-probing the same blots with either ␤-tubulin or ERK2 antibodies, as indicated. (30,46). The molecular details of these events are just beginning to unfold, but both of these effects by 1,25(OH) 2 D 3 require VDR (47).…”

mentioning

confidence: 99%

Extracellular Calcium-sensing Receptor Activation Induces Vitamin D Receptor Levels in Proximal Kidney HK-2G Cells by a Mechanism That Requires Phosphorylation of p38α MAPK

Maiti

Hait

Beckman

2008

Journal of Biological Chemistry

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2؉ ] e concentration in the physiological range is capable of directly increasing renal proximal VDR expression, and the induction mechanism requires activation of the CaSR and signal mediation by the p38␣ MAP kinase pathway.Extracellular ionized calcium [Ca 2ϩ ] e is a critical mediator of cell signaling for the storage and release of both parathyroid hormone (PTH) 2 and calcitonin. Homeostasis of [Ca 2ϩ ] e is important to proper neuromuscular contractions, cellular integrity, and the deposition of mineral in skeletal structures (1). A multi-organ system coordinates and maintains [Ca 2ϩ ] e homeostasis within a narrow physiological range (2). Activation of the an extracellular calcium sensing receptor (CaSR) when [Ca 2ϩ ] e concentrations are high maintains the storage form of PTH in the parathyroid gland (3,4). Release of PTH from the parathyroid gland is a direct result of a decrease in serum [Ca 2ϩ ] e (5, 6). PTH is a potent stimulus of 1,25-dihydroxyvitamin D 3 (1,25(OH) 2 D 3 ) biosynthesis in the kidney proximal convoluted tubule by its induction of 1␣-hydoxylation (7). Resultant increase in [Ca 2ϩ ] e by 1,25(OH) 2 D 3 regulates PTH at two levels; where CaSR signaling shuts down PTH secretion (8, 9) and 1,25(OH) 2 D 3 through transactivation of its nuclear receptor (VDR) inhibits prepro-PTH transcription (10).[Ca 2ϩ ] e is also a potent mediator of the balance between cellular proliferation and differentiation while VDR mediates biological functions of 1,25(OH) 2 D 3 and is expressed in many different cell types (11). Past work has focused on the role of VDR in mineral homeostasis, with VDR activators used mainly to treat hyperparathyroidism secondary to chronic kidney disease (12). A more recent perspective includes the use of vitamin D analogs in combination with calcimimetics and phosphate binders in the management of hyperparathyroid disorders (13). It is therefore important to identify the mechanisms whereby CaSR signaling and VDR activation coincide in the tissues that co-express these two receptors. We previously reported for the first time that [Ca 2ϩ ] e is a direct regulator of VDR in proximal human kidney . The present study was designed to better explore the mechanism by which [Ca 2ϩ ] e influences VDR increase in these cells.PTH exerts several actions in the renal proximal tubule that include control of phosphate transport and induction of 1,25(OH) 2 D 3 -1␣-hydroxylase (CYP27B1) mRNA (15-17). The receptor for PTH is a another member of the GPCR family capable of coordinating bidirectional signaling through pathways involving adenylate cyclase or activation of protein kinase C depending on the concentration of PTH and the specific cell type (18,19). In proximal tubule epithelial cells, PTH stimulates 1␣-hydroxylation, mediates 1,25(OH) 2 D 3 -24-hydroxylase (CYP24) down-regulation and represses 1,25(OH) 2 D 3 -receptor (VDR) transcription all by increasing cAMP and activating the cAMP-dependent response element-binding protein (CREB) (20 -22). However, the set of ...

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Determinants of circulating 1,25-dihydroxyvitamin D3 levels: the role of renal synthesis and catabolism of vitamin D

Cited by 46 publications

References 14 publications

Low Serum Levels of 25-Hydroxyvitamin D Predict Fatal Cancer in Patients Referred to Coronary Angiography

Low Serum Levels of 25-Hydroxyvitamin D Predict Fatal Cancer in Patients Referred to Coronary Angiography

Role of vitamin D in immune responses and autoimmune diseases, with emphasis on its role in multiple sclerosis

Extracellular Calcium-sensing Receptor Activation Induces Vitamin D Receptor Levels in Proximal Kidney HK-2G Cells by a Mechanism That Requires Phosphorylation of p38α MAPK

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