Phorbol 12-myristate 13-acetate and 1,25-dihydroxyvitamin D3 regulate 1,25-dihydroxyvitamin D3 receptors synergistically in rat osteosarcoma cells. 1994

T A Reinhardt, and R L Horst
U.S. Department of Agriculture, Agricultural Research Service, National Animal Disease Center, Ames, IA 50010-0070, USA.

In this study, we examined the effect of activation of protein kinase C (PKC) pathways on the regulation of 1,25-dihydroxyvitamin D receptors (VDR) in rat osteosarcoma (ROS) 17/2.8 cells. Activation of PKC with phorbol 12-myristate 13-acetate (PMA) resulted in a time- and dose-dependent increase in VDR expression in ROS cells. Treatment of ROS cells with 4alpha-phorbol 12,13-dedeconate, a PKC-inactive phorbol ester, had no effect on VDR expression. Oleoyl acetyl glycerol (OAG), a synthetic diacylglycerol, stimulated VDR up-regulation in ROS cells. The PKC inhibitors (H-7, staurosporin, and sphingosine) all blocked PMA-mediated up-regulation of VDR in a dose-dependent manner. We next examined the interaction of 1,25(OH)2D3 and PKC activation by PMA on the regulation of VDR in ROS cells. We found that PMA or 1,25(OH)2D3 treatment alone resulted in a 50 and 200% increase in VDR, respectively. PMA treatment alone resulted in a 50% increase in VDR protein and a marginal 20% increase in VDR mRNA. 1,25(OH)2D3 up-regulation of VDR was associated with a 2-fold increase in VDR mRNA. In contrast, co-treatment of ROS cells with PMA and 1,25(OH)2D3 resulted in a synergistic 10-fold induction of VDR mRNA and the appearance of a 7.2 kb VDR transcript. VDR protein was also synergistically up-regulated by combined PMA and 1,25(OH)2D3 treatment of ROS cells. Scatchard analysis demonstrated that the synergistic effect of PMA and 1,25(OH)2D3 on VDR protein expression was not associated with any change in the affinity of VDR for 1,25(OH)2D3. The synergistic effect of 1,25(OH)2D3 and PMA on VDR expression supports a link between PKC signal pathways and the function of VDR.

UI MeSH Term Description Entries
D002117 Calcitriol The physiologically active form of vitamin D. It is formed primarily in the kidney by enzymatic hydroxylation of 25-hydroxycholecalciferol (CALCIFEDIOL). Its production is stimulated by low blood calcium levels and parathyroid hormone. Calcitriol increases intestinal absorption of calcium and phosphorus, and in concert with parathyroid hormone increases bone resorption. 1 alpha,25-Dihydroxycholecalciferol,1 alpha,25-Dihydroxyvitamin D3,1, 25-(OH)2D3,1,25(OH)2D3,1,25-Dihydroxycholecalciferol,1,25-Dihydroxyvitamin D3,1 alpha, 25-dihydroxy-20-epi-Vitamin D3,1,25(OH)2-20epi-D3,1,25-dihydroxy-20-epi-Vitamin D3,20-epi-1alpha,25-dihydroxycholecaliferol,Bocatriol,Calcijex,Calcitriol KyraMed,Calcitriol-Nefro,Decostriol,MC-1288,MC1288,Osteotriol,Renatriol,Rocaltrol,Silkis,Sitriol,Soltriol,Tirocal,1 alpha,25 Dihydroxyvitamin D3,1,25 Dihydroxycholecalciferol,1,25 Dihydroxyvitamin D3,1,25 dihydroxy 20 epi Vitamin D3,Calcitriol Nefro,D3, 1 alpha,25-Dihydroxyvitamin,D3, 1,25-Dihydroxyvitamin,D3, 1,25-dihydroxy-20-epi-Vitamin,KyraMed, Calcitriol,MC 1288
D004357 Drug Synergism The action of a drug in promoting or enhancing the effectiveness of another drug. Drug Potentiation,Drug Augmentation,Augmentation, Drug,Augmentations, Drug,Drug Augmentations,Drug Potentiations,Drug Synergisms,Potentiation, Drug,Potentiations, Drug,Synergism, Drug,Synergisms, Drug
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012516 Osteosarcoma A sarcoma originating in bone-forming cells, affecting the ends of long bones. It is the most common and most malignant of sarcomas of the bones, and occurs chiefly among 10- to 25-year-old youths. (From Stedman, 25th ed) Sarcoma, Osteogenic,Osteogenic Sarcoma,Osteosarcoma Tumor,Osteogenic Sarcomas,Osteosarcoma Tumors,Osteosarcomas,Sarcomas, Osteogenic,Tumor, Osteosarcoma,Tumors, Osteosarcoma
D013755 Tetradecanoylphorbol Acetate A phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA. Phorbol Myristate Acetate,12-Myristoyl-13-acetylphorbol,12-O-Tetradecanoyl Phorbol 13-Acetate,Tetradecanoylphorbol Acetate, 4a alpha-Isomer,12 Myristoyl 13 acetylphorbol,12 O Tetradecanoyl Phorbol 13 Acetate,13-Acetate, 12-O-Tetradecanoyl Phorbol,Acetate, Phorbol Myristate,Acetate, Tetradecanoylphorbol,Myristate Acetate, Phorbol,Phorbol 13-Acetate, 12-O-Tetradecanoyl,Tetradecanoylphorbol Acetate, 4a alpha Isomer
D014407 Tumor Cells, Cultured Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely. Cultured Tumor Cells,Neoplastic Cells, Cultured,Cultured Neoplastic Cells,Cell, Cultured Neoplastic,Cell, Cultured Tumor,Cells, Cultured Neoplastic,Cells, Cultured Tumor,Cultured Neoplastic Cell,Cultured Tumor Cell,Neoplastic Cell, Cultured,Tumor Cell, Cultured
D015398 Signal Transduction The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. Cell Signaling,Receptor-Mediated Signal Transduction,Signal Pathways,Receptor Mediated Signal Transduction,Signal Transduction Pathways,Signal Transduction Systems,Pathway, Signal,Pathway, Signal Transduction,Pathways, Signal,Pathways, Signal Transduction,Receptor-Mediated Signal Transductions,Signal Pathway,Signal Transduction Pathway,Signal Transduction System,Signal Transduction, Receptor-Mediated,Signal Transductions,Signal Transductions, Receptor-Mediated,System, Signal Transduction,Systems, Signal Transduction,Transduction, Signal,Transductions, Signal
D051381 Rats The common name for the genus Rattus. Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus
D018167 Receptors, Calcitriol Proteins, usually found in the cytoplasm, that specifically bind calcitriol, migrate to the nucleus, and regulate transcription of specific segments of DNA with the participation of D receptor interacting proteins (called DRIP). Vitamin D is converted in the liver and kidney to calcitriol and ultimately acts through these receptors. Calcitriol Receptors,Cholecalciferol Receptors,Receptors, Vitamin D,Vitamin D 3 Receptors,Vitamin D Receptors,1,25-Dihydroxycholecalciferol Receptor,1,25-Dihydroxycholecalciferol Receptors,1,25-Dihydroxyvitamin D 3 Receptor,1,25-Dihydroxyvitamin D3 Receptor,1,25-Dihydroxyvitamin D3 Receptors,Calcitriol Receptor,Receptors, 1,25-Dihydroxyvitamin D 3,Receptors, Cholecalciferol,Receptors, Vitamin D 3,Receptors, Vitamin D3,Vitamin D 3 Receptor,Vitamin D Receptor,Vitamin D3 Receptor,Vitamin D3 Receptors,1,25 Dihydroxycholecalciferol Receptor,1,25 Dihydroxycholecalciferol Receptors,1,25 Dihydroxyvitamin D 3 Receptor,1,25 Dihydroxyvitamin D3 Receptor,1,25 Dihydroxyvitamin D3 Receptors,D Receptor, Vitamin,D Receptors, Vitamin,D3 Receptor, 1,25-Dihydroxyvitamin,D3 Receptor, Vitamin,D3 Receptors, 1,25-Dihydroxyvitamin,D3 Receptors, Vitamin,Receptor, 1,25-Dihydroxycholecalciferol,Receptor, 1,25-Dihydroxyvitamin D3,Receptor, Calcitriol,Receptor, Vitamin D,Receptor, Vitamin D3,Receptors, 1,25-Dihydroxycholecalciferol,Receptors, 1,25-Dihydroxyvitamin D3

Related Publications

T A Reinhardt, and R L Horst
July 1984, The Journal of biological chemistry,
T A Reinhardt, and R L Horst
August 1995, The Biochemical journal,
T A Reinhardt, and R L Horst
January 2016, Journal of clinical and diagnostic research : JCDR,
Copied contents to your clipboard!