Phorbol 12-myristate 13-acetate is a PKC-activating phorbol ester, increases the intracellular Ca2+ concentration ([Ca2+]i) in a dose-dependent manner, with an EC50 of 11.7 nM.
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Protein kinase C (PKC) is a key molecule involved in cell growth, apoptosis, and differentiation. Phorbol 12-Myristate 13-Acetate (PMA) is an activator of certain types of PKC, including group A and group B isoforms[3]. Stimulation with 1 μM PMA for 3 min resulted in promoted nucleotide exchange activity in 293T cells[4]. In differentiated Caco-2 cells, pretreatment with 100 nM PMA for 5 min followed by 2h incubation with 10 nM 1,25(OH)2D3 resulted in a 2.6-fold increase in hCYP24A1 mRNA level compared to cells treated by 1,25(OH)2D3 alone. Incubation with 100 nM PMA for 30 min resulted in the activation of ERK1/2 and p38 kinase in Caco-2 cells, whereas pretreatment with the MEK inhibitor U0126 at 10, 20 or 100 μM completely inhibited ERK1/2 activation by PMA and partially suppressed PMA-induced p38 kinase activation. Cells pre-treated with 10 μM U0126 or 8 μM p38 kinase inhibitor SB202190 showed reduced enhancing effect of PMA on 1,25(OH)2D3-induced hCYP24A1 promoter activity[5]. In both W/Wv genetically mast cell-deficient mice and congenic normal mice, repeated administration of PMA (5 μg, 3 times per week for 6 weeks) to the ear skin remarkably increased the number of dermal mast cells[6].
作用机制
PMA is a phorbol ester structurally analogous to diacylglycerol. It activates PKC isoforms by associating with their C1 domains[7].
Germany
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Dortmund, Germany, 44139
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University Medical Center Leipzig, Department of Medical Psychology and Medical Sociology, Section Psychosocial Oncology
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