Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:4.1.1.17 (ornithine decarboxylase)
 6,351 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Studies described herein were designed to examine the effects of 12-O-tetradecanoyl phorbol-13-acetate (TPA), and a Ca2+ ionophore (ionomycin), singly or in combination, on the activation and expression of the Ca(2+)-dependent protein kinase C (PKC) isoenzymes (alpha, beta and gamma) at the protein and messenger RNA (mRNA) levels in T cells. These two agents induce the activation and proliferation of T lymphocytes by mimicking the action of inositol phospholipid-derived second messengers normally generated by triggering of the antigen-specific T-cell receptor (TcR)/CD3 complex. TPA-induced T-cell proliferation, expression of interleukin-2 receptor-alpha subunit (IL-2R alpha) and transferrin receptor, CD3 down-regulation and, lastly, the cytosol-to-membrane PKC translocation (determined by an enzymatic assay or by immunoblotting with a cross-reactive anti-PKC peptide antibody) were all facilitated by ionomycin. Immunoblots with isoenzyme-specific anti-PKC monoclonal antibodies demonstrated expression of immunoreactive PKC alpha, PKC beta and PKC gamma proteins that were translocated to the membrane upon TPA plus ionomycin stimulation. Resting T cells expressed abundant levels of mRNA for PKC alpha and PKC beta, but very low levels (relative to brain) of PKC gamma. TPA increased by two- to threefold the expression of PKC beta, but not of PKC alpha or PKC gamma, mRNA within 12 hr of stimulation. Ionomycin synergized with TPA in increasing the expression of PKC alpha and PKC beta mRNA. The two agents also synergized in inducing expression of additional activation/growth-associated genes, namely the c-myc protooncogene, ornithine decarboxylase (ODC) and IL-2R alpha. Ionomycin alone was inactive (or marginally active) in all of these assays. The translocation of distinct Ca(2+)-dependent PKC isoenzymes to the membrane and the up-regulation of PKC alpha and beta mRNA suggest that at least these two isoenzymes are involved in discrete steps of the pathway leading to T-cell activation and proliferation. Moreover, the combined effects of TPA and ionomycin on T-cell function and cell-surface antigen expression appear to be due, at least in part, to their synergistic activation of distinct PKC isoenzyme(s).
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PMID:Phorbol ester synergizes with Ca2+ ionophore in activation of protein kinase C (PKC)alpha and PKC beta isoenzymes in human T cells and in induction of related cellular functions. 138 36

The drug DL-alpha-difluoromethylornithine (DFMO), a specific inhibitor of ornithine decarboxylase, was studied as an antitrypanosomal drug. We showed that an antibody response to the surface antigen of trypanosomes was necessary for rapid elimination of parasites after DFMO treatment, as effects of drug treatment were greatly reduced in immunosuppressed mice. Efficacy of the treatment also varied with the inherent ability of different mouse strains to mount antibody responses to trypanosomal surface antigen. Further, some trypanosomes were more resistant to the combined effects of drug and host immunity, as relapses occurred with certain parasite clones.
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PMID:Role of antibody in the elimination of trypanosomes after DL-alpha-difluoromethylornithine chemotherapy. 642 94

Pneumocystis carinii pneumonia remains a prevalent opportunistic disease among immunocompromised individuals. Although aggressive prophylaxis has decreased the number of acute P. carinii pneumonia cases, many patients cannot tolerate the available drugs, and experience recurrence of the infection, which can be fatal. It is now generally agreed that the organism should be placed with the fungi, but the identification of extant fungal species representing its closest kins, remains debated. Most recent data indicate that P. carinii represents a diverse group of organisms. Since the lack of methods for the continuous subcultivation of this organism hampered P. carinii research, molecular cloning and nucleotide sequencing approaches led the way for understanding the biochemical nature of this pathogen. However, within the last 5 years, the development of improved protocols for isolating and purifying viable organisms from infected mammalian host lungs has enabled direct biochemical and metabolism studies on the organism. The protein moiety of the major high mol. wt surface antigen, represented by numerous isoforms, is encoded by different genes. These proteins are post-transcriptionally modified by carbohydrates and lipids. The organism has the shikimic acid pathway that leads to the formation of compounds which mammals cannot synthesise (e.g., folic acid), hence drugs that inhibit these pathways are effective against the pathogen. Ornithine decarboxylase has now been detected; rapid and complete depletion of polyamines occurs in response to difluoromethylornithine (DFMO). Instead of ergosterol (the major sterol of higher fungi), P. carinii synthesises distinct delta7, C-24-alkylated sterols. An unusual C32 sterol, pneumocysterol, has been identified in human-derived P. carinii. Another signature lipid discovered is cis-9,10-epoxy stearic acid. CoQ10, identified as the major ubiquinone homologue, is synthesised de novo by P. carinii. Atovaquone and other hydroxynaphthoquinone drugs with anti-P. carinii activity probably inhibit pathogen respiration as CoQ analogues. Unlike its effects on Plasmodium, atovaquone does not inhibit the P. carinii dihydroorotate dehydrogenase and pyrimidine metabolism.
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PMID:Pneumocystis carinii pneumonia: the status of Pneumocystis biochemistry. 950 36

Polyamines (PA) and retinoic acid affect mammalian cell growth, differentiation and apoptosis. Retinoic acid induces granulocytic differentiation of mieloid cell lines and, during this process, is responsible for the expression of CD11b, a surface antigen. In this study we investigate the effects of retinoic acid on HL-60 cells, monitoring ornithine decarboxylase (ODC) activity (enzyme rate of PA), putrescine (PUT), spermidine (SPD), spermine (SPM) levels, CD11b myeloid surface marker differentiation, cell cycle, and apoptosis. ODC activity and PUT levels are correlated with mieloid cell differentiation induced by retinoic acid treatment. Only the ODC/PUT ratio is connected with retinoic acid treated HL-60 cells. Treated cultures show a decrease of proliferation and a cell block in the G0/G1 phase, with consequent diminished S phase. The G0/G1 and S phases are significantly related to ODC activity and to PUT and SPD behavior, whereas in differentiating condition only the decrease of PUT is related to the S phase. CD11b expression, stimulated by retinoic acid treatment, is associated with the SPM trend. Total PA behavior agrees with apoptotic cell increase after 96 h of stimulation. Our data show that retinoic acid treatment modifies ODC activity and the turnover of PA. PUT, SPD and SPM, therefore, have a different role, and may be involved in the differentiative/apoptotic program of retinoic acid treated HL-60 cells.
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PMID:Ornithine decarboxylase, polyamines and CD11b expression in HL-60 cells during differentiation induced by retinoic acid. 1527 23