Vitamin D receptor is not required for the rapid actions of 1,25‐dihydroxyvitamin D<sub>3</sub> to increase intracellular calcium and activate protein kinase C in mouse osteoblasts

Wali, Ramesh K.; Kong, Juan; Sitrin, Michael D.; Bissonnette, Marc; Li, Yan Chun

doi:10.1002/jcb.10432

Cited by 66 publications

(31 citation statements)

References 39 publications

(31 reference statements)

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“…It is well known that the biological effects of nuclear receptors are characterised by nuclear transcriptional regulation of gene expression as well as non-genomic effects. We have recently proposed that rosiglitazone activates basal glucose uptake in a manner dependent on p38MAPK [19], and in some cellular systems PKC phosphorylation has been found to be increased by other nuclear receptor agonists such as vitamin D analogues [31]. The effect of NR1HR agonists on Slc2a4 expression in rat brown adipocytes is in agreement with the up-regulation of Slc2a4 detected in murine and human adipocytes, where the Slc2a4 promoter is a direct transcriptional target for the NR1HR/RXR heterodimer [8,13].…”

Section: Discussionsupporting

confidence: 75%

Liver X receptor agonists ameliorate TNFα-induced insulin resistance in murine brown adipocytes by downregulating protein tyrosine phosphatase-1B gene expression

et al. 2006

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Aims/hypothesis The nuclear receptors, including nuclear receptor subfamily 1, group H, member 3 (NR1HR, also known as liver X receptor [LXR]), are sensors of cholesterol metabolism and lipid biosynthesis that have recently been proposed as insulin sensitisers. TNFα has been described as a link between obesity and the development of insulin resistance, an important contributor to the pathogenesis of type 2 diabetes. Therefore, we decided to investigate the ability of NR1HR agonists to ameliorate TNFα-induced insulin resistance in brown adipocytes. Methods Primary brown adipocytes from rat fetuses, and from wild-type neonate mice and neonate mice deficient in the gene encoding protein tyrosine phosphatase-1B (Ptpn1, also known as Ptp1b) were cultured in the absence or presence of TNFα and different nuclear receptor agonists. Among them, the unrelated NR1HR ligands T0901317, GW3965 and (22R)-hydroxycholesterol were tested. After insulin stimulation, glucose uptake and solute carrier family 2 (facilitated glucose transporter), member 4 (SLC2A4, formerly known as GLUT4) translocation were measured. Next the insulin signalling cascade was determined by submitting cells to lysis, immunoprecipitation and immunoblotting. Results NR1HR agonists ameliorate TNFα-induced insulin resistance restoring completely insulin-stimulated glucose uptake and SLC2A4 translocation to plasma membrane. This effect is parallel to the recovery of the insulin cascade insulin receptor/IRS-2/phosphatidylinositol 3-kinase/protein kinase B, and could be due to the fact that T0901317 prevents the increase of PTPN1 production and phosphatase activity produced by TNFα. In this regard, Ptpn1-deficient brown adipocytes showed protection against insulin resistance by TNFα. Moreover, we observed that T0901317 produced in itself a significant increase over basal glucose uptake consistent with an increase of SLC2A4 protein content in plasma membrane, attributable to the activation of protein kinase ζ and/or the increase of Slc2a4 expression. Conclusions/interpretation Nuclear receptors NR1HR are interesting potential targets for drug treatment of insulin resistance. Keywords

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Section: Discussionsupporting

confidence: 75%

Liver X receptor agonists ameliorate TNFα-induced insulin resistance in murine brown adipocytes by downregulating protein tyrosine phosphatase-1B gene expression

et al. 2006

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“…Antibodies to a membrane protein identified by Nemere et al (16) block the ability of 1,25-D to induce rapid calcium uptake and activation of PKC in cartilage cells. VDRϪ/Ϫ osteoblasts take up calcium and activate PKC similar to the wild-type osteoblasts, implicating proteins other than VDR in these actions (17). In contrast, Gniadecki (18) has described activation of ERK through 1,25-D-induced activation of Raf as a result of interactions between VDR and the adaptor protein Shc.…”

mentioning

confidence: 99%

The Functional Consequences of Cross-talk between the Vitamin D Receptor and ERK Signaling Pathways Are Cell-specific

Narayanan

Sepúlveda

Falzon

et al. 2004

Journal of Biological Chemistry

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(8), and other cellular and physiological processes. Many of the actions of 1,25-D are mediated by an intracellular receptor, the vitamin D receptor (VDR), a member of the steroid/thyroid receptor superfamily of ligandregulated transcription factors (9, 10). The activity of VDR is dependent not only on the concentration of receptor and hormone but also on its heterodimer partner, retinoid X receptor (RXR), and the coactivator proteins that bind to the VDR and facilitate transcription of target genes (11).In addition to its actions as a modulator of transcription through activation of the VDR, 1,25-D can rapidly activate cell signaling cascades independent of a requirement for transcription (12-14). The means by which 1,25-D induces these changes has not been fully elucidated. Rapid activation of extracellular signal-regulated kinases, ERK1/ERK2 in NB4 promyelocytic leukemia cells can be induced not only by 1,25-D, but also by analogs that are unable to activate VDR, suggesting the possibility of a separate receptor (15). Antibodies to a membrane protein identified by Nemere et al. (16) block the ability of 1,25-D to induce rapid calcium uptake and activation of PKC in cartilage cells. VDRϪ/Ϫ osteoblasts take up calcium and activate PKC similar to the wild-type osteoblasts, implicating proteins other than VDR in these actions (17). In contrast, Gniadecki (18) has described activation of ERK through 1,25-D-induced activation of Raf as a result of interactions between VDR and the adaptor protein Shc. VDR-null osteoblasts do not exhibit ion channel responses in response to 1,25-D (13) and Erben et al. (14) have reported that deletion of the VDR DNA binding domain also eliminates non-genomic responses. Thus some of the rapid actions of 1,25-D may be dependent upon VDR, whereas others are not.Nuclear receptor family members including VDR and RXR as well as many of their coactivators, are phosphoproteins whose activities are also regulated by cell signaling pathways (19 -27). Thus 1,25-D can modulate VDR activity both through direct binding to VDR as well as by altering the kinase activities within the cell (9,11,12,28). Although VDR has not been reported to be a substrate for ERK, RXR␣ (one of the three RXR isoforms) (29) is phosphorylated by ERK, as are some of the VDR coactivators including SRC-1 (30).To better understand the functional interactions between VDR and the ERK signaling pathway, we sought to determine whether 1,25-D activates ERK in the osteoblastic cell lines, MG-63 and MC3T3-E1, and to evaluate the effects of ERK on VDR activity. We found that 1,25-D rapidly induced ERK activity and that this activation persisted at 24 h in both cell lines. Surprisingly, the effects of ERK activation on VDR activity in the two cell lines were very different. Overexpression of Raf-1 (an upstream activator of ERK) reduced VDR activity in MC3T3-E1 cells, but stimulated activity in MG-63 cells.

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“…As mentioned in the considerations above, rapid responses to calcitriol exist: within minutes after administration, calcitriol increases intestinal calcium transport and activates protein kinase C in FW fish (Nemere et al 2000) and mammals (Boyan et al 1999, Wali et al 2003. Larsson et al (2003) conducted binding studies to enterocyte membrane receptors for calcitriol in rainbow trout (Oncorhynchus mykiss), a close relative of salmon.…”

Section: From Fw To Sw: Increasing Calcitriol and Decreasing Svdrmentioning

confidence: 99%

The vitamin D receptor and its ligand 1α,25-dihydroxyvitamin D3 in Atlantic salmon (Salmo salar)

Lock¹,

Ørnsrud²,

Aksnes

et al. 2007

Journal of Endocrinology

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Seaward migration of Salmo salar is preceded by preparatory physiological adaptations (parr-smolt transformation) to allow for a switch from freshwater (FW) to seawater (SW), which also means a switch in ambient calcium from hypocalcic (!1 mM Ca 2C ) to the plasma (w1 . 25 mM Ca 2C ) and to strongly hypercalcic (8-12 mM Ca 2C ). Uptake, storage (skeleton, scales) and excretion of calcium need careful regulation. In fish, the vitamin D endocrine system plays a rather enigmatic role in calcium physiology. Here, we give direct evidence for calcitriol involvement in SW migration. We report the full sequence of the nuclear vitamin D receptor (sVDR0) and two alternatively spliced variants resulting from intron retention (sVDR1 and sVDR2). In FW parr, SW adapting smolts, and in SW adults, plasma concentrations of 25(OH)D 3 and 24,25(OH) 2 D 3 did not change significantly. Plasma calcitriol concentrations were lowest in FW parr, doubled during smoltification and remained elevated in SWadults. Increased calcitriol coincided with a twofold decrease in sVDR mRNA levels in gill, intestine, and kidney of FW smolts and SW adults, when compared with parr. Clearly, there was a negative feedback and dynamic response of the vitamin D endocrine system during parr-smolt transformation. The onset of these dynamic changes in FW parr warrants a further search for the endocrines that initiate these changes. We speculate that the vitamin D system plays a crucial role in calcium and phosphorus handling in Atlantic salmon.

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Vitamin D receptor is not required for the rapid actions of 1,25‐dihydroxyvitamin D₃ to increase intracellular calcium and activate protein kinase C in mouse osteoblasts

Cited by 66 publications

References 39 publications

Liver X receptor agonists ameliorate TNFα-induced insulin resistance in murine brown adipocytes by downregulating protein tyrosine phosphatase-1B gene expression

Liver X receptor agonists ameliorate TNFα-induced insulin resistance in murine brown adipocytes by downregulating protein tyrosine phosphatase-1B gene expression

The Functional Consequences of Cross-talk between the Vitamin D Receptor and ERK Signaling Pathways Are Cell-specific

The vitamin D receptor and its ligand 1α,25-dihydroxyvitamin D3 in Atlantic salmon (Salmo salar)

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Vitamin D receptor is not required for the rapid actions of 1,25‐dihydroxyvitamin D3 to increase intracellular calcium and activate protein kinase C in mouse osteoblasts

Cited by 66 publications

References 39 publications

Liver X receptor agonists ameliorate TNFα-induced insulin resistance in murine brown adipocytes by downregulating protein tyrosine phosphatase-1B gene expression

Liver X receptor agonists ameliorate TNFα-induced insulin resistance in murine brown adipocytes by downregulating protein tyrosine phosphatase-1B gene expression

The Functional Consequences of Cross-talk between the Vitamin D Receptor and ERK Signaling Pathways Are Cell-specific

The vitamin D receptor and its ligand 1α,25-dihydroxyvitamin D3 in Atlantic salmon (Salmo salar)

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Vitamin D receptor is not required for the rapid actions of 1,25‐dihydroxyvitamin D₃ to increase intracellular calcium and activate protein kinase C in mouse osteoblasts