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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

2012; Elsevier BV; Volume: 1823; Issue: 10 Linguagem: Inglês

10.1016/j.bbamcr.2012.06.023

1879-2596

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

Stress Responses and Cortisol

The involvement of calcium-mediated signaling pathways in the mechanism of action of 1α,25-dihydroxyvitamin D3 (1,25D) is currently demonstrated. In this study we found that 1,25D induces nongenomic effects mediated by membrane vitamin D receptor (VDRm) by modulating intermediate filament (IF) phosphorylation and calcium uptake through L-type voltage-dependent calcium channels (L-VDCC) in cerebral cortex of 10 day-old rats. Results showed that the mechanism of action of 1,25D involves intra- and extracellular calcium levels, as well as the modulation of chloride and potassium channels. The effects of L-VDCCs on membrane voltage occur over a broad potential range and could involve depolarizing or hyperpolarizing coupling modes, supporting a cross-talk among Ca2 + uptake and potassium and chloride channels. Also, the Na+/K+-ATPase inactivation by ouabain mimicked the 1,25D action on 45Ca2 + uptake. The Na+/K+-ATPase inhibition observed herein might lead to intracellular Na+ accumulation with subsequent L-VDCC opening and consequently increased 45Ca2 + (calcium, isotope of mass 45) uptake. Moreover, the 1,25D effect is dependent on the activation of the following protein kinases: cAMP‐dependent protein kinase (PKA), Ca2 +/calmodulin‐dependent protein kinase (PKCaMII), phosphatidylinositol 3‐kinase (PI3K) and mitogen‐activated protein kinase p38 (p38MAPK). The modulation of calcium entry into neural cells by the 1,25D we are highlighting, might take a role in the regulation of a plethora of intracellular processes. Considering that vitamin D deficiency can lead to brain illness, 1,25D may be a possible candidate to be used, at least as an adjuvant, in the pharmacological therapy of neuropathological conditions.