Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:4.1.1.17 (
ornithine decarboxylase
)
6,351
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Treatment of EL-4 lymphoma cells with tetradecanoylphorbol-acetate (TPA), a well-known activator of protein kinase C, induces the production of the
T cell growth factor
interleukin-2 (IL-2) and the expression of IL-2-specific mRNA within 4-8 h. This system is an ideal model for studies on the induction of a differentiated function in a homogeneous lymphoid cell population by a defined signal. TPA induces also an increase of
ornithine decarboxylase
(
ODC
) activity and elevates the intracellular concentrations of putrescine and polyamines within 4-8 h. A similar increase of intracellular putrescine and polyamine concentrations can be achieved by administration of 2 mM putrescine to the culture medium. However, putrescine cannot induce the production of IL-2 in the absence of TPA and cannot reconstitute the IL-2 production in cultures with PGE2 or cyclosporine A, i.e., two well-known immunosuppressive substances which inhibit
ODC
activity. Putrescine has rather a counter-regulatory effect as concluded from the observation that the TPA-induced
TCGF
production and IL-2-specific mRNA expression are augmented (superinduced) by the
ODC
inhibitor D,L-alpha-difluoromethylornithine (DFMO) and again suppressed after the administration of putrescine or polyamines to DFMO-treated cultures. The glycolytic activity, general protein synthesis [( 3H]leucine incorporation), and the cell cycle progression from G2/M to G1, in contrast, are inhibited by DFMO and reconstituted by putrescine. This demonstrates that the cells are able to sacrifice to a large extent several vital functions including their general protein synthesis and to devote themselves at the same time to a fulminant production of their functionally most relevant protein IL-2. This process is downregulated by
ODC
and its product putrescine. A correlation between increased IL-2 production and accumulation of cells in the G2/M phase was also observed in cultures treated with hydroxyurea or with a combination of amethopterin and adenosine.
...
PMID:Downregulation of T cell growth factor production by ornithine decarboxylase and its product putrescine: D,L-alpha-difluoromethylornithine suppresses general protein synthesis but augments simultaneously the production of interleukin-2. 249 71
Ornithine decarboxylase
(
ODC
) is the initial enzyme in polyamine synthesis. An increase in
ODC
activity is associated with increased RNA, DNA, and protein synthesis. We have used the induction of
ODC
by mitogens and alloantigens in human peripheral blood lymphocytes as an intracellular marker of protein synthesis and lymphocyte activation. The immunosuppressive agent cyclosporine was found to inhibit both the mitogen and alloantigen stimulated induction of
ODC
in lymphocytes in a manner that parallels inhibition of subsequent 3H-thymidine incorporation. When purified T lymphocytes were stimulated with mitogen alone, minimal
ODC
activity was detected. The addition of 5% monocytes, human Interleukin-1 (IL-1), or
T cell growth factor
(IL-2) enhanced mitogen-induced
ODC
activity in T lymphocytes 4-10-fold. Cyclosporine inhibited the induction of
ODC
when T lymphocytes were combined with monocytes or growth factors. We conclude that (1) the induction of
ODC
in human lymphocytes by mitogen and alloantigen is inhibited in the presence of cyclosporine; (2) the induction of
ODC
activity in purified T lymphocytes requires the presence of both mitogen and monocytes or their products; (3) IL-1 and IL-2 can supplement for monocytes and augment the phytohemagglutinin induction of
ODC
in T lymphocytes; and (4) cyclosporine inhibits
ODC
induction in T lymphocytes stimulated with mitogen in the added presence of monocytes, IL-1, or IL-2. The inhibition of
ODC
induction and polyamine synthesis by cyclosporine adds insight into its mode of action on the mechanisms involved in early T cell activation.
...
PMID:The effect of cyclosporine on ornithine decarboxylase induction with mitogens, antigens, and lymphokines. 623 49
