1α,25-Dihydroxyvitamin D3 mechanism of action: Modulation of L-type calcium channels leading to calcium uptake and intermediate filament phosphorylation in cerebral cortex of young rats

Zanatta, Leïla; Goulart, Paola Bez; Gonçalves, Renata; Pierozan, Paula; Duarte, Elisa Cristiana Winkelmann; Woehl, Viviane Mara; Pessoa-Pureur, Regina; Silva, Fátima Regina Mena Barreto; Zamoner, Ariane

doi:10.1016/j.bbamcr.2012.06.023

Cited by 67 publications

(45 citation statements)

References 97 publications

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“…Administration of calcitriol has been shown to downregulate L-type calcium channels [8] by phosphorylating the intermediate filaments of cells that express the channels [42]. This effect appears to be dose-dependent; at low concentrations, calcitriol administration results in the decreased expression of L-type calcium channel mRNA and lower measured current through the channels, resulting in a neuroprotective effect on hippocampal neurons.…”

Section: Vitamin D and The Injured Brainmentioning

confidence: 99%

Vitamin D and Its Role in Neonatal Hypoxic-Ischemic Brain Injury

Stessman

Peeples

2018

Neonatology

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Emerging evidence has demonstrated that vitamin D plays an important role in many adult neurologic disorders, but is also critical in neuronal development and pruning in the neonatal and pediatric populations. Neonates are at a particularly high risk of vitamin D deficiency, in part due to the high prevalence of maternal deficiency during pregnancy. Several preclinical studies have demonstrated that infants born to vitamin D-deficient mothers are at a high risk of developing neonatal brain injury, and recent clinical studies have shown that neonates with hypoxic-ischemic encephalopathy (HIE) tend to be vitamin D-deficient. There are limited data, however, on whether additional prenatal or postnatal supplementation may alter the prevalence or severity of neonatal HIE. This review examines the current data supporting the neuroprotective role of vitamin D, with a focus on how these findings may be translated to neonates with HIE.

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Section: Vitamin D and The Injured Brainmentioning

confidence: 99%

Vitamin D and Its Role in Neonatal Hypoxic-Ischemic Brain Injury

Stessman

Peeples

2018

Neonatology

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“…In turn, VDR can bind to retinoic X receptor to serve as a nuclear transcription factors, regulating the expression of numerous genes. In addition to these genomic responses, calcitriol can mediate rapid responses by binding to cell membrane VDR, interacting with ion channels (Menegaz et al, 2011; Zanatta et al, 2012; Tamayo et al, 2017) and membrane-based signaling pathways (Larriba et al, 2014). …”

Section: Introductionmentioning

confidence: 99%

Calcitriol, the Bioactive Metabolite of Vitamin D, Increases Ventricular K+ Currents in Isolated Mouse Cardiomyocytes

et al. 2018

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Calcitriol, the bioactive metabolite of vitamin D, interacts with the ubiquitously expressed nuclear vitamin D receptor (VDR) to induce genomic effects, but it can also elicit rapid responses via membrane-associated VDR through mechanisms that are poorly understood. The down-regulation of K+ currents is the main origin of electrophysiological remodeling in pathological hypertrophy and heart failure (HF), which can contribute to action potential prolongation and subsequently increase the risk of triggered arrhythmias. Adult mouse ventricular myocytes were isolated and treated with 10 nM calcitriol or vehicle for 15–30 min. In some experiments, cardiomyocytes were pretreated with the Akt inhibitor triciribine. In the adult mouse ventricle, outward K+ currents involved in cardiac repolarization are comprised of three components: the fast transient outward current (Itof), the ultrarapid delayed rectifier K+ current (Ikur), and the non-inactivating steady-state outward current (Iss). K+ currents were investigated using the whole-cell or the perforated patch-clamp technique and normalized to cell capacitance to obtain current densities. Calcitriol treatment of cardiomyocytes induced an increase in the density of Itof and Ikur, which was lost in myocytes isolated from VDR-knockout mice. In addition, calcitriol activated Akt in cardiomyocytes and pretreatment with triciribine prevented the calcitriol-induced increase of outward K+ currents. In conclusion, we demonstrate that calcitriol via VDR and Akt increases both Itof and Ikur densities in mouse ventricular cardiomyocytes. Our findings may provide new mechanistics clues for the cardioprotective role of this hormone in the heart.

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“…For example, it increases the expression genes codifying growth factors such as Nerve growth factor (NGF), glial cell line-derived neurotrophic factor (GDNF), NT3, and enzymes involved in the synthesis of neurotransmitters (tyrosine hydroxylase, tryptophan hydroxylase 2, and glutamate decarboxylase), whereas it decreases expression of voltage-dependent calcium channel [3,79]. VDR is also expressed in the caveolae and induces nongenomic effects that include activation of cAMP-dependent protein kinase (PKA), Ca 2+ /calmodulin-dependent protein kinase, phosphatidylinositol 3-kinase, and mitogen-activated protein kinase p38 leading to phosphorylation of neurofilaments, modulation of chloride, potassium, and voltage-dependent calcium channel in rat cortical neurons [80]. In addition, 25-hydroxylase and 1-a-hydroxylase activity are also found in the nervous tissue.…”

Section: Vitamin D In Nervous System Physiology Neuroprotection Andmentioning

confidence: 99%

Vitamin D and Sphingolipids: Role in Bone and Neural System

Frati¹,

Gil²,

Pierucci³

et al. 2017

A Critical Evaluation of Vitamin D - Basic Overview

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Abstract1-Alpha,25-dihydroxyvitamin D3 (1,25(OH) 2 D 3 ) is known to play an important physiological role on growth and differentiation in a variety of nonmalignant and malignant cell types through classical actions, mediated by its specific receptor (VDR), and nongenomic actions resulting in the activation of specific signalling pathways. Due to the broad distribution of Vitamin D Receptor (VDR) in many tissues and the ability of 1,25(OH) 2 D 3 to regulate fundamental processes, such as cell proliferation and differentiation, this steroid hormone has been suggested in the treatment of different diseases, from cancer to neurodegenerative diseases. In fact, structural 1,25(OH) 2 D 3 analogues, with weaker collateral effects, have recently entered in clinical trials. Other interesting molecules due to their pleiotropic actions are the bioactive sphingolipids (SLs), in particular ceramide (Cer) and sphingosine 1-phosphate (S1P). Cells maintain a dynamic balance of these metabolites since Cer and sphingoid bases mediate cell death, while S1P exerts mitogenic effects and promotes differentiation of several cell types including osteogenic and neural cells. The biological actions of 1,25(OH) 2 D 3 and SLs, in particular S1P, share many common effectors, including calcium regulation, growth factor expression, inflammatory cytokines, etc., but whether they could act synergistically is still unknown and deserves further investigation.

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1α,25-Dihydroxyvitamin D3 mechanism of action: Modulation of L-type calcium channels leading to calcium uptake and intermediate filament phosphorylation in cerebral cortex of young rats

Cited by 67 publications

References 97 publications

Vitamin D and Its Role in Neonatal Hypoxic-Ischemic Brain Injury

Vitamin D and Its Role in Neonatal Hypoxic-Ischemic Brain Injury

Calcitriol, the Bioactive Metabolite of Vitamin D, Increases Ventricular K+ Currents in Isolated Mouse Cardiomyocytes

Vitamin D and Sphingolipids: Role in Bone and Neural System

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