Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.13 (protein kinase C)
 49,245 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated possible interaction of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] and PTH on: 1) proliferation (monolayer culture) and colony formation (agarose stabilized suspension cultures); 2) expression of 1,25-(OH)2D3 receptor (VDR); and 3) cAMP response to PTH, using primary cultures of chondrocytes from rat tibia proximal epiphysis. 1 alpha,25-(OH)2D3 stereospecifically stimulated DNA synthesis, cell counts, and colony formation at low concentration (10(-12) M). Within 6 h bovine PTH (bPTH)(1-34), human PTH (hPTH)(28-48) (10(-10) M), (Bu)2cAMP (1-2 mM), and 12-O-tetradecanoyl-13-acetate (10(-8) M) increased [3H]thymidine incorporation in the absence and presence of 1,25-(OH)2D3. Both PTH fragments also stimulated chondrocyte growth and colony formation in a Ca-dependent fashion. Prolonged exposure to bPTH(1-34) or hPTH(28-48) did not affect baseline DNA synthesis but increased the stimulatory effect of 1,25-(OH)2D3. This increase was inhibited in the presence of H7 (inhibition of PKC) or the monoclonal hPTH(1-38) antibody A1-70. In subconfluent chondrocyte cultures VDR was up-regulated by bPTH(1-34) and hPTH(28-48) (10(-10) M) or activators of protein kinase C (PKC), but not by (Bu)2cAMP. It was blocked by cycloheximide and actinomycin D and persisted in the presence of Ca-channel blockers. Inhibition of PKC by H7 also blocked the effect of bPTH(1-34) on VDR. The cAMP response to bPTH(1-34) was not affected by 1,25-(OH)2D3. We conclude that: 1) DNA synthesis, cell proliferation, and colony formation in chondrocyte monolayer or suspension cultures is increased by aminoterminal and midregional PTH fragments and by cAMP analogs in a Ca- dependent fashion; 2) bPTH(1-34) and hPTH(28-48) up-regulate VDR by cAMP-independent, PKC-dependent steps requiring transcriptional and translational processes; both PTH fragments also amplify the effect of 1,25-(OH)2D3 on DNA synthesis; and 3) no difference is found between the bPTH(1-34) and hPTH(28-48) fragments with respect to chondrocyte proliferation and VDR up-regulation, although the two differ with respect to stimulation of cAMP production.
 ...
PMID:Synergistic effects of parathyroid hormone and 1,25-dihydroxyvitamin D3 on proliferation and vitamin D receptor expression of rat growth cartilage cells. 752 93

Primary chondrocytes from quail embryo epiphysis (quail epiphyseal chondrocytes, QEC) can grow either in suspension or in monolayer. In this study, the adhesion of QEC to collagen II was used as a model to study the regulation of the ligand-binding activity of integrin receptors that allows these cells to undergo a rapid transition from suspension to an adherent state. Preincubation of suspension QEC (QECSP) with the disintegrin echistatin increased by 40% their adhesion to collagen II. An inverse relationship between immobilized collagen density and echistatin-induced increase of chondrocyte adhesion was observed, thus suggesting that the disintegrin acts by increasing the ligand-binding affinity of collagen receptor(s). Further, echistatin activity does not appear to depend upon a direct binding of the disintegrin to collagen receptor(s). In fact, immobilized anti-beta1 antibodies, but not immobilized echistatin, served as effective binding sites for QECSP. Echistatin failed to stimulate chondrocyte adhesion to collagen in the presence of metabolic inhibitors, while an activating anti-beta1 antibody was still effective. Thus, echistatin may promote cell adhesion by interfering with energy-dependent signals that keep the collagen receptor(s) in a low-affinity state. Adhesion experiments performed in the presence of pharmacological inhibitors indicate that phosphatidyl inositol 3-kinase (PI3-K)/protein kinase C (PKC) and protein kinase A (PKA) pathways may transmit opposing signals on chondrocyte adhesion, and that collagen receptors are kept in a low-affinity state by PI3-kinase/PKC signalling. Since echistatin is a high-affinity ligand for alphavbeta3 integrin, the effect of the function-blocking anti-alphavbeta3 antibody LM609 was investigated. Like echistatin, LM609 stimulated chondrocyte adhesion to collagen and failed to support their attachment. Therefore, our data suggest that alphavbeta3-antagonists might regulate the binding activity of the beta1 collagen receptor, which in turn leads to the rapid transition of chondrocytes from suspension to an adherent state.
 ...
PMID:Modulation of chondrocyte adhesion to collagen by echistatin. 1627 Jul 51