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)

This study focused on the effects of tacalcitol (1,24 (R) (OH)2D3, TV-02) ointment (20 micro g/g) on cutaneous inflammation, epidermal proliferation, and differentiation and compared them with tacalcitol ointment (2 micro g/g) and other anti-psoriatic ointments using hairless mice. Tacalcitol ointment (0, 2 and 20 micro g/g) significantly inhibited 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced cutaneous inflammation, histopathologically. The effect of tacalcitol ointment (20 micro g/g) on cutaneous inflammation was much stronger than that of tacalcitol ointment (0, 2 micro g/g), and as effective as calcipotriol ointment (50 micro g/g) or betamethasone valerate ointment (1.2 mg/g). Tacalcitol ointment (20 micro g/g) also significantly inhibited TPA-induced myeloperoxidase (MPO) activity, as effectively as calcipotriol ointment (50 micro g/g) or betamethasone valerate ointment (1.2 mg/g). The effect of tacalcitol ointment on epidermal proliferation [ornithine decarboxylase (ODC) activity] and differentiation [transglutaminase (TGase) activity] was dose-dependent from 0 micro g/g to 20 micro g/g. The effect of tacalcitol ointments on epidermal proliferation was significant at the doses of 2 micro g/g and 20 micro g/g, and that on epidermal differentiation was significant at the doses of 0.2 micro g/g or more. The effect of tacalcitol ointment (20 micro g/g) on epidermal differentiation was significantly stronger than tacalcitol ointment (2 micro g/g). In this study, tacalcitol ointment (20 micro g/g) was found to have a marked effect on cutaneous inflammation and improved effect on epidermal differentiation, although tacalcitol ointment (2 micro g/g) also had significant effects on epidermal proliferation and differentiation. These findings support the clinical effectiveness of tacalcitol ointment (20 micro g/g) against psoriasis.
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PMID:Pharmacological profiles of high-concentration (20 microg/g) tacalcitol ointment: effects on cutaneous inflammation, epidermal proliferation, and differentiation in mice. 1292 40

Mutation of the Kirsten-ras (Ki-ras) proto-oncogene occurs frequently in colorectal cancers. alpha-Difluoromethylornithine (DFMO), an irreversible inhibitor of the polyamine biosynthetic enzyme, ornithine decarboxylase (ODC), inhibits Ki-ras transformation and colon tumorigenesis in carcinogen-treated animal models by mechanisms yet to be elucidated. Caco-2 cells transfected with an activated Ki-ras, but not parental cells, formed tumors in severe combined immunodeficient (SCID) mice. DFMO treatment (2% in drinking water) prevented tumor growth. Gene expression profiling was performed to identify Ki-ras-and DFMO-dependent patterns of gene expression. Microarray results were validated with real-time or semi-quantitative RT-PCR and/or Western blot analysis. Genes upregulated in Caco-2 cells expressing an activated Ki-ras encoded cytoskeletal-, transport-, protease-, and gap junction-associated proteins. These genes are important for normal development and maintenance of colonic epithelial tissue. Caco-2 cells transfected with an activated Ki-ras displayed increased expression of the integrin alpha 1 (INGA1) and enhanced cell migration on laminin. These parameters were unaffected by DFMO, but Ki-ras-dependent migration was inhibited by INGA1 antibodies. Other Ki-ras-dependent, but DFMO-independent, genes included transglutaminase (TGase) and kallikrein 6 (KLK6). Ki-ras-transfected cells also expressed increased levels of connexin43 (Cx43) (RNA and protein), tight junction protein, and endothelin 1. DFMO reversed these increases. The results indicated that the Ki-ras oncogene caused changes in experimental cell migration and cell-cell communication genes and that some of these changes could be reversed by DFMO.
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PMID:The chemopreventive agent alpha-difluoromethylornithine blocks Ki-ras-dependent tumor formation and specific gene expression in Caco-2 cells. 1505 74

We have recently demonstrated the inverse correlation between transglutaminase (TGase) activity and DNA synthesis in periportal hepatocytes (PPH) and perivenous hepatocytes (PVH) at 1 d after partial hepatectomy. In order to elucidate a role of polyamines as substrates of TGase in the differential growth capacities between PPH and PVH from regenerating liver, we investigated the zonal differences in alteration of ornithine decarboxylase (ODC) activity and polyamines. In two subpopulations, the inverse correlation between DNA synthesis and epsilon-(gamma-glutamyl) lysine (Gln-Lys) cross-linking catalyzed by TGase was demonstrated at 1 d after partial hepatectomy. ODC activity in PPH significantly increased with a peak at 1 d after partial hepatectomy, whereas did not in PVH. Protein-binding SPD in PPH also transiently increased with a peak at 1 d after partial hepatectomy, but did not in PVH. These results suggest that at 1 d after partial hepatectomy, in PPH, the inhibition of Gln-Lys cross-linking by the formation of N-gamma-glutamyl SPD leads to the increase of DNA synthesis, whereas in PVH, enhanced formation of Gln-Lys cross-linking leads to the lower DNA synthesis.
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PMID:The involvement of polyamines as substrates of transglutaminase in zonal different hepatocyte proliferation after partial hepatectomy. 1568 97

Ornithine decarboxylase (ODC) is the rate-limiting enzyme of polyamine synthesis. Polyamines and ODC are connected to cell proliferation and transformation. Resting cells display a low ODC activity while normal, proliferating cells display fluctuations in ODC activity that coincide with changes in the actin cytoskeleton during the cell cycle. Cancerous cells display constitutively elevated ODC activity. Overexpression of ODC in NIH 3T3 fibroblasts induces a transformed phenotype. The cytoskeletal rearrangements during cytokinesis and cell transformation are intimately coupled to the ODC activity but the molecular mechanisms have remained elusive. In this study we investigated how ODC and polyamines influence the organization of the cytoskeleton. Given that the small G-proteins of the rho family are key modulators of the actin cytoskeleton, we investigated the molecular interactions of rhoA with ODC and polyamines. Our results show that transglutaminase-catalyzed polyamination of rhoA regulates its activity. The polyamination status of rhoA crucially influences the progress of the cell cycle as well as the rate of transformation of rat fibroblasts infected with temperature-sensitive v-src. We also show that ODC influences the intracellular distribution of rhoA. These findings provide novel insights into the mechanisms by which ODC and polyamines regulate the dynamics of the cytoskeleton during cell proliferation and transformation.
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PMID:Ornithine decarboxylase regulates the activity and localization of rhoA via polyamination. 1933 12


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