Cellular redox state and activating protein-1 are involved in ascorbate effect on calcitriol-induced differentiation |
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Authors: | G López-Lluch M -V Blázquez R Pérez-Vicente A Macho M I Burón F J Alcaín E Muñoz P Navas |
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Institution: | (1) Laboratorio Andaluz de Biología, Universidad Pablo de Olavide, Carretera de Utrera, Km 1.0, 41013 Sevilla, Spain;(2) Departamento de Biología Celular, Fisiología e Inmunología, Universidad de Córdoba, Córdoba;(3) Departamento de Biologá Vegetal, Facultad de Ciencias, Universidad de Córdoba, Córdoba |
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Abstract: | Summary Ascorbate has been related to the differentiation of several mesenchymal cells including haematopoietic cells. We have previously demonstrated that ascorbate enhances the activity of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) on monocytic differentiation of HL-60 cells. Here, we show that ascorbate-mediated modification of cellular redox state and AP-1 (activating protein-1) DNA binding during early phases are related to the enhancing effect of ascorbate on differentiation. Ascorbate, but not its fully oxidized form, dehydroascorbate, or an ascorbate analogue with a low rate of oxidation, ascorbate-2-phosphate, enhanced the differentiation induced by 1,25(OH)2D3, modified cytosolic reactive oxygen species levels and mitochondrial redox potential (m), and modulated AP-1 DNA binding in HL-60 cells. Ascorbate itself increased AP-1 binding to DNA in noninduced cells, whereas it inhibited AP-1 binding in 1,25(OH)2D3-induced cells. However, ascorbate increased the mRNA levels ofc-jun, junB. andc-fos in 1,25(OH)2D3-induced cells. Taken together, these results suggest that the enhancing effect of ascorbate on HL-60 differentiation induced by 1,25(OH)2D3 is related to its effect on the cellular redox state and the modulation of AP-1 activity.Abbreviations 1,25-(OH)2D3
1,25-dihydroxyvitamin D3
- m
mitochondrial transmembrane potential
- AP-1
activating protein-1
- Asc-2-P
ascorbate-2-phosphate
- DHA
dehydroascorbate
- DiOC6(3)
3,3-dihexyloxacarboxyanine iodide
- EMSA
electromobility shift assay
- NBT
nitroblue tetrazolium
- ROS
reactive oxygen species |
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Keywords: | Leukemia Cell differentiation Ascorbic acid Vitamin D Activating protein-1 Redox regulation |
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