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)
MRL-lpr/lpr is a strain of mice that develops spontaneous signs of the autoimmune disease, systemic lupus erythematosus (SLE or lupus). The lpr (lymphoproliferation) defect has been identified as an insertion of an early transposon (ETn) derived sequence into the
fas
apoptosis gene. We studied the in vivo effects of difluoromethylornithine (DFMO), an irreversible inhibitor of the polyamine biosynthetic enzyme,
ornithine decarboxylase
(
ODC
), on the expression of
fas
in MRL-lpr/lpr mice as well as in congenic MRL- + / + and autoimmune NZB/W strains. Using Northern blot hybridization and reverse transcription polymerase chain reaction (RT-PCR), we found that DFMO treatment resulted in an increase in the expression of
fas
mRNA in the thymus of MRL-lpr/lpr mice. Using RT-PCR, we further found that the increased expression of
fas
was associated with the suppression of chimeric ETn/
fas
mRNA. With fractionated CD4 + and CD8 + T cells, we found a cell-specific effect of DFMO on chimeric ETn/
fas
expression in CD8 + cells. ETn/
fas
expression was detected in CD8+ T cells from untreated mice, but it was eliminated after DFMO treatment. HPLC analysis of polyamines showed depletion of putrescine and partial reduction of spermidine (35%) in DFMO-treated mice compared to controls. These results indicate that DFMO-mediated polyamine depletion is linked to the regulation of
fas
and chimeric ETn/
fas
in MRL-lpr/lpr mice. Elevated levels of polyamines in this strain, as found in earlier studies, may be associated with the progression of the autoimmune disease by altering the expression of
fas
gene or by facilitating the expression of chimeric ETn/
fas
. Our data also provide new mechanistic insights into the beneficial effects of DFMO on these mice.
...
PMID:Polyamine-fas interactions: inhibition of polyamine biosynthesis in MRL-lpr/lpr mice is associated with the up-regulation of fas mRNA in thymocytes. 1043 86
