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  • Title: Involvement of protein kinase C in 1,25(OH)2-vitamin D3 regulation of calcium uptake by cultured myocytes.
    Author: Marinissen MJ, Selles J, Boland R.
    Journal: Cell Signal; 1994 Jul; 6(5):531-8. PubMed ID: 7818989.
    Abstract:
    1,25-Dihydroxyvitamin D3 [1,25(OH)2D3] produces an acute stimulation of calcium influx in cultured chick embryo myocytes through activation of voltage-gated Ca2+ channels and involvement of cyclic AMP-dependent protein kinase A (PKA). To investigate the participation of protein kinase C (PKC) in this hormone-induced response, calcium uptake was measured in myocytes treated with PKC activators 12-O-tetradecanoyl phorbol 13-acetate (TPA, 50 nM) or 1,2-dioctanoyl-rac-glycerol (DOG, 50 microM). TPA and DOG decreased 45Ca2+ uptake 37% below control cultures. Contrarily, the PKC inhibitors H7 and staurosporine increase myocyte Ca2+ uptake 51% and 54%, respectively. In addition, PKC activity was augmented in cytosol (39%) and membranes (31%) of myocytes after 5 min of treatment with 0.1 nM 1,25(OH)2D3. Likewise, the hormone induced a fast biphasic formation of diacylglycerol, the natural PKC activator, peaking at 30 s (26%) and 3 min (39%). On the other hand, the stimulation of Ca2+ uptake induced by compound H7 as well as 1,25(OH)2D3 was completely abolished with a specific PKA inhibitor. H7 also produced an increase in cAMP levels (172%) and PKA activity (204%). These results suggest the participation of PKC in 1,25(OH)2D3 regulated calcium influx in heart cells and the operation of a cross-talk mechanism between the PKC and PKA pathways.
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