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

We compared L-phenylalanine mustard (L-PAM)-induced cytotoxicity and DNA cross-linking with and without a 42-h preincubation with the ornithine decarboxylase inhibitor alpha-difluoromethylornithine (DFMO, 1 mM) in a human lymphoma cell line. The combination showed increased toxicity with a Do ratio of 1.6. L-PAM-induced DNA protein cross-linking as measured by alkaline elution was not altered by a DFMO pretreatment. DNA interstrand cross-linking was increased when L-PAM-treated cells were pretreated with DFMO. The differences occurred between 12 and 24 h following the L-PAM treatment. Peak protein cross-linking occurred 6 h following L-PAM removal with or without DFMO pretreatment. While peak interstrand cross-linking occurred 6 h following L-PAM removal, the DFMO-pretreated cells maintained higher cross-link levels longer than did control cells. The increase in interstrand cross-linking seen in DFMO-pretreated cells was maintained at several different L-PAM doses. The increased cytotoxicity could not be accounted for by the increased cross-linking alone. We have postulated that DFMO pretreatment results in a delay in the appearance of a cross-link removal system. The differences seen between results using these human cells and previous reports using rodent cells are discussed.
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PMID:Effect of alpha-difluoromethylornithine on L-phenylalanine mustard-induced cytotoxicity and DNA interstrand cross-linking in a human cell line in vitro. 308 Feb 30

The immunosuppressive peptide cyclosporin A (CyA) is an extremely effective therapy for severe recalcitrant psoriasis, although its mechanism of action is unknown. In this study, we examined the effect of CyA on keratinocyte growth and cytokine expression, and showed that CyA inhibits the growth of murine and human keratinocytes (KC) and KC cell lines. In addition, CyA inhibits the expression of cytokine genes in a dose-dependent fashion. After 2 days' incubation with 20 microM CyA, interleukin-1 alpha (IL-1 alpha), interleukin-1 beta (IL-1 beta), and interleukin 8 (IL-8) mRNA were decreased by 4-fold, 3.3-fold and 3.3-fold, respectively, in COLO-16, a keratinocyte cell line. IL-1 biological activity recovered from COLO-16 culture supernatants decreased to one-fifth of that of controls. In the murine KC cell line PAM 212, 10 microM CyA treatment for 2 days downregulated IL-1 alpha, tumour necrosis factor-alpha (TNF-alpha) and IL-1 receptor by 60%, but had no effect on the message for interleukin 3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), ornithine decarboxylase and beta-actin. Cells cultured for 5 days in the presence of CyA required much lower concentrations (2 microM) to achieve the same degree of inhibition of IL-1 alpha. Similar tissue concentrations of CyA have been reported in psoriatics undergoing CyA therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cyclosporin A inhibits keratinocyte cytokine gene expression. 814 71