Disease relevance of Leucaenine

• We applied this protocol to study the effect of the plant amino acid mimosine on the rate of replicon initiation in exponentially growing murine erythroleukemia F4N cells [1].
• However, mimosine does not influence folate metabolism in SH-SY5Y neuroblastoma [2].
• Our results demonstrated that mimosine inhibits DNA synthesis in mitochondrial, nuclear, and simian virus 40 (SV40) genomes to a similar extent [3].
• Agents that produced double-strand breaks in DNA and/or inhibition of transcription caused an induction of p53 in the absence of radiation in control cells but not in ataxia-telangiectasia, but inhibitors of cell cycle progression such as mimosine and aphidicolin led to an increase in p53 in both cell types in the absence of radiation [4].
• Mimosine-treated neural precursor cells injected into established intracerebral CNS-1 gliomas in nude mice migrated extensively throughout the tumor and into the surrounding parenchyma beyond the tumor over 3 days [5].

High impact information on Leucaenine

• L-Mimosine suppressed the posttranslational hydroxylation of the precursors for collagen and for eukaryotic initiation factor-5A (eIF-5A) by directly inhibiting the specific protein hydroxylases involved, prolyl 4-hydroxylase (E.C. 1.14.11.2) and deoxyhypusyl hydroxylase (E.C. 1.14.99.29), respectively [6].
• Cells that have escaped from mimosine G1 arrest, from hydroxyurea or aphidicolin S-phase arrest, or from VM-26-induced G2 arrest subsequently have all the hallmarks of mitosis--such as a mitotic microtubule array, nuclear envelope breakdown, and chromatin condensation [7].
• Here we demonstrate that G(1)/S arrest by overexpression of the cyclin-dependent kinase inhibitors p16(INK4a), p21(Cip1), or p27(Kip1) or by treatment with mimosine or aphidicolin confers anoikis resistance in MCF-10A cells [8].
• Unexpectedly, UVC treatment was also found to block the induction of p21Waf1 by various stress-inducing agents such as mimosine in the p53-deficient cells [9].
• Mimosine, however, enhanced p21(Waf1/Cip1) expression, completely inhibited RKO cell proliferation, and exerted marked protection against a subsequent PGA2 challenge [10].

Chemical compound and disease context of Leucaenine

• The effects of mimosine on folate metabolism were investigated in human MCF-7 cells and SH-SY5Y neuroblastoma [2].
• pyd genes of Rhizobium sp. strain TAL1145 are required for degradation of 3-hydroxy-4-pyridone, an aromatic intermediate in mimosine metabolism [11].
• We now report that the alpha-hydroxypyridones, specifically mimosine, a natural product, and deferiprone, an experimental drug, inhibited deoxyhypusyl hydroxylase in T-lymphocytic and promonocytic cell lines and, in a concentration-dependent manner, suppressed replication of HIV-1 [12].
• In this study, we compared the effects of mimosine to desferrioxamine (DFO), a well-characterized iron chelator, and found that both chemicals similarly altered cell cycle progression in MDA-MB-453 human breast cancer cells [13].
• The intraperitoneal administration of L-mimosine (200 microg/dose) to the potassium permanganate treated mice for 5 consecutive days (the first at the same time of inoculation of the KMnO4), produced a significant decrease in size and weight of the granuloma when compared to mice not treated with L-mimosine (controls) [14].

Biological context of Leucaenine

• We have examined the effects of mimosine on cell cycle traverse in the mimosine [corrected]-resistant CHO cell line CHOC 400 [15].
• Initiation of DNA replication in the dihydrofolate reductase locus is confined to the early S period in CHO cells synchronized with the plant amino acid mimosine [16].
• The results suggest that in addition to inhibiting the elongation step of DNA synthesis, mimosine inhibits the initiation of DNA replication as well [1].
• The plant amino acid mimosine has been shown to reversibly arrest mammalian cells in late G1 phase of the cell cycle [17].
• In summary, the cell cycle-blocking drug mimosine does not appear to affect the rate of apoptosis in the regressing rat ventral prostate gland [18].

Anatomical context of Leucaenine

• Addition of mimosine to cycling epithelial cells halted cell cycle traverse in S phase, coincident with an inhibition of p34cdc2 histone H1 kinase activity [19].
• Mimosine treatment eliminated MRE- and Sp1-binding activity in nuclear extracts from MCF-7 cells but not in nuclear extracts from a mimosine-resistant cell line, MCF-7/2a [20].
• Nuclei isolated from mimosine-arrested HeLa cells initiate semiconservative DNA replication upon incubation in cytosolic extracts from proliferating human cells [21].
• MCF-7 cells cultured in the presence of 350 microm mimosine were growth-arrested, whereas mimosine had no effect on SH-SY5Y cell proliferation [2].
• Moreover, overexpression of Cdk2 reversed the inhibition of centrosome duplication by mimosine treatment [22].

Associations of Leucaenine with other chemical compounds

• Phosmidosine acts at an earlier point in G1 compared with mimosine or aphidicolin, well-known cell cycle blockers at the G1-S boundary [23].
• Mimosine and aphidicolin did not inhibit the expression of cyclin A or p34cdc2, whereas all three reagents inhibited expression of cyclin B. Low concentrations of the protein inhibitor cycloheximide inhibited release of the quercetin but not the mimosine or aphidicolin block [24].
• Although many studies have demonstrated that the iron chelators mimosine and deferoxamine inhibit DNA replication in mammalian cells, their mechanism of action remains controversial [2].
• The gly- cell line is still sensitive to mimosine, suggesting that the drug may inhibit both the mitochondrial and the cytosolic forms [25].
• In contrast to aphidicolin, mimosine did not inhibit DNA replication in lysates of mammalian cells supplied with exogenous deoxyribonucleotide triphosphate precursors for DNA synthesis [3].

Gene context of Leucaenine

• Cell fractionation shows that cyclins A, E, and Cdk2 are bound to nuclei from mimosine-arrested cells [21].
• In this study, the mechanism for mimosine-induced inhibition of SHMT1 transcription was elucidated [20].
• In addition, G(1) arrest induced by mimosine reduced AML1 protein levels [26].
• However, cells infected by wild-type virus and blocked from entering S phase by addition of mimosine still show a p53 response [27].
• p21WAF1/CIP1/SDI1 is elevated through a p53-independent pathway by mimosine [28].

Analytical, diagnostic and therapeutic context of Leucaenine

• A mimosine-responsive transcriptional element was localized within the first 50 base pairs of the human SHMT1 promoter by deletion analyses and gel mobility shift assays [20].
• The DNA content of nuclei isolated from mimosine-treated cells was determined by flow cytometry [29].
• Microinjection of mimosine into 4-cell embryos had no visible effect on development during the first 3 days after fertilization [30].
• Functionally, the PHD inhibitor l-mimosine (l-Mim, 50 mg.kg(-1).day(-1) ip for 2 wk) substantially upregulated HIF-1alpha expression in the kidneys, especially in the renal medulla, and remarkably enhanced (by >80%) the natriuretic response to renal perfusion pressure in Sprague-Dawley rats [31].
• Simultaneous enantioseparations of 15 racemic aromatic amino acids and L-mimosine for their chiral discrimination were achieved by neutral selector-modified capillary electrophoresis (CE) and by charged selector-modified CE [32].

References