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)

Flow cytometry and the fluorescent dyes DCF and R123 were used to examine oxygen metabolite production in human leukocytes and T-lymphoblastoid Jurkat cells, activated by PMA or by FMLP. When unseparated leukocytes were activated by PMA, oxidative products were generated not only in PMN and monocytes but also to a lower extent in lymphocytes. These responses were correlated with protein kinase C activation. PMA did not, however, induce the synthesis of reactive oxygen species in isolated lymphocytes. FMLP did not affect lymphocyte oxidative metabolism when added to the whole leukocyte mixture, but activated only the phagocyte populations. Similarly, Jurkat cells which alone were unresponsive to PMA, became strongly fluorescent when they were mixed with PMN and treated with this activator. In all cases, they did not respond to FMLP. Superoxide dismutase and catalase addition did not prevent the lymphoid cell response in the presence of phagocytes, whereas Desferal did. These data indicate that under physiological conditions, activated lymphocytes are capable of oxidative metabolism and also evidence some close relation between the leukocyte populations. We discuss the putative mechanism of oxygen metabolite generation in lymphocytes and the role of these metabolites in the immune response.
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PMID:Increased oxidative metabolism in PMA-activated lymphocytes: a flow cytometric study. 151 80

We found that 4-beta-phorbol 12-myristate 13-acetate (PMA) caused decreased expression of the polymorphonuclear neutrophil (PMN) surface antigen 31D8. In contrast to the rapid initiation of the oxidative burst caused by PMA, the effect was slow to start but increased during incubation periods up to 50 min. To study this apparent protein kinase C-independent late effect of PMA, we measured 31D8 expression in PMNs after incubation with various concentrations of PMA. The maximum PMA-induced inhibition was 76 +/- 2%, with an ID50 of 3.9 +/- 0.4 ng/ml. Oxidants and prooxidants (hydrogen peroxide, hypochlorite, taurine-chloramine, and ferrous iron, with or without H2O2) had no direct effect on 31D8 antigen expression. The following substances were not protective against the inhibitory affect of PMA: (1) antioxidants (superoxide dismutase, catalase, azide, dimethyl sulfoxide, Desferal, and ascorbate, with the exception of alpha-tocopherol), (2) inhibitors of protein kinase C (H7 and W7), (3) inhibitors of 5-lipoxygenase (A-63162, MK886, and high-dose indomethacin) and (4) inhibitors of cyclooxygenase (low-dose indomethacin). Myeloperoxidase-deficient PMNs had normal 31D8 antigen expression and a decrease of 31D8 antigen expression by PMA, as did normal PMNs. The inactive analog of PMA, 4-alpha-phorbol didecanoate, had no effect on 31D8 antigen expression. alpha-Tocopherol (50 micrograms/ml) and betamethasone (150 micrograms/ml) protected against the PMA effect by 30.5 +/- 7.3 (P less than .0005) and 52 +/- 15 (P less than 0.004) channels, respectively. These results indicate that PMA has a protein kinase C-independent late effect on human neutrophils, which can be prevented by pretreatment with alpha-tocopherol or the steroid betamethasone. These compounds probably exert their protective effect by membrane stabilization.
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PMID:Characterization of a direct effect of phorbol myristate acetate on human neutrophil cell membrane using 31D8 monoclonal antibody. 154 11

A short and a long fibre sample of amosite asbestos were tested for their effects on cells of the human Type 2 alveolar epithelial cell-line A549 in vitro. The long amosite sample was found to cause a rapid detachment of the epithelial cells live from their substratum. At the highest dose, on average 28% of the cells present were detached in this way. Studies on the mechanism of the detachment injury showed that it did not involve oxidants since it was not ameliorated by scavengers of active oxygen species. Neither was the effect reduced by treatment of the fibres with the iron chelator Desferal. Treatments reported to increase the interaction between fibres and cells, serum and poly-L-lysine, did not influence the detachment injury, nor did lung lining fluid. Conversely, the fibronectin tripeptide RGD alone could cause detachment which suggested that a fibronectin-binding integrin was involved. This receptor could be reduced in activity by long fibre exposure, leading to detachment. The detaching effect of fibre could be mimicked by the protein kinase C activator PMA, and so the second messenger system of the cell could also be involved. This type of injury could be important in the pathology associated with exposure to long fibres.
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PMID:Asbestos fibre length-dependent detachment injury to alveolar epithelial cells in vitro: role of a fibronectin-binding receptor. 839 59

Iron regulatory proteins (IRPs) are RNA-binding proteins that post-transcriptionally regulate synthesis of iron uptake (transferrin receptor) and storage (ferritin) proteins. Our previous work demonstrating that IRP1 is phosphorylated by protein kinase C supported the hypothesis that factors in addition to iron modulate IRP function. We have investigated changes in activity and expression of both IRP1 and IRP2 during phorbol 12-myristate 13-acetate (PMA)-induced differentiation of HL-60 cells. In contrast to IRP1, IRP2 was highly phosphorylated in untreated cells. PMA stimulated phosphorylation of IRP1 and IRP2 by at least 2-3-fold without affecting incorporation of [35S]methionine into the proteins. IRP1 and IRP2 isolated from PMA-treated cells displayed different phosphopeptides. Phosphorylation of IRPs was associated with a 2-fold increase in high affinity RNA binding activity without altering KD, and this was accompanied by a 50% increase in transferrin receptor mRNA abundance. PMA acted on a latent pool of binding activity that is present in a nonaconitase oxidized form and is largely composed of a stable but inactive species of IRP2. Desferal and hemin modulated iron-responsive element binding activity in HL-60 cells without affecting the phosphorylation state of IRP1. Hemin appeared to reduce the abundance of phosphorylated IRP2. Thus, multiple factors affect the function of both IRPs and indicate that extracellular agents may program changes in cellular iron metabolism by altering the phosphorylation state of these regulatory RNA-binding proteins.
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PMID:Phosphorylation and activation of both iron regulatory proteins 1 and 2 in HL-60 cells. 863 54