Toxic action of mimosine—I. Inhibition of mitosis and DNA synthesis of H.Ep-2 cell by mimosine and 3,4-dihydroxypyridine

Tsai, Wei-Chong; Ling, Kuo-Huang

doi:10.1016/0041-0101(71)90076-6

Cited by 40 publications

(36 citation statements)

References 8 publications

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“…DOHH inhibition, for 16 h resulted in the loss of only a few polysomal bangs relative to control polysomes (Criterion I), but did not affect the presence of these bands in the monosomai and/or free mRNA pool (Criterion lla-c). This finding confirms that mimosine does not stop mRNA synthesis in general [33]. Even if bands disappeared from the polysomes (Criterion I) and also vanished from the cytoplasm (Criterion IId), certain bands reappeared within 30 rain of release from mimosine (Criterion lID, as shown in panel 3 of Fig.…”

Section: Resultssupporting

confidence: 72%

Detection of a sub‐set of polysomal mRNAs associated with modulation of hypusine formation at the G1‐S boundary Proposal of a role for eIF‐5A in onset of DNA replication

et al. 1995

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S phase entry, I.e. start of DNA replication, Is a crucial step in proliferation. Inhibition of S phase entry correlates with Inbibition of hypusine formation, an event affecting only the eukaryotie Initiation factor $A (elF4A), Its hypuslnecontalning sequence wus postulated to authorize polysomal utilization of specific trauscripts for proteins necessary to enable DNA replication. Using ndmodne to reversibly suppress the hyposinc-forming deoxyhypusyi hydmxylase (E.C. 1.1¢99.29) in cells while differentially displaying their polysomal versus non-polysemal mRNA popolations, we report the detection and cla~!fleation of several mRNA species that indeed disappear from and reappear at !lo1-ysomes in con~rt with inhibition and d_!s!nhibition, respectively, of hypusine formation. Based on initial sequence data, two trauslationally controlled enzymes, both critical for proliferation, are identified us candicate wodncts of such mRNAs, methionine adenosyitrausferuse (E.C 2.$.1.6) and cytochrome-c oxiduse 0gC 1.9.3.1) subunit 1. The existence of such potative hyposinedependent messenger nnclde adds (/O, mas) prevides the basis for a proposal on their molecular function in onset of multiplication.Key words: Post-translational modification; eIF-5A; Hypusine; Cell cycle control; Translational control; mRNA I, IntroductionThe unique amino acid hypusine [~-(4-amino-2(R).hydroxybutyl)-t.-lysine] is formed post-translationally by the sequential action of deoxyhypusyl synthase (DOHS) and deoxyhypusyl hydroxylase (DOHH) on a single lysyl residue in only one cellular protein, the eukaryotic initiation factor 5A (elF-SA) [I-3]. The hypusine-containing domain shows remarkable interspecies conservation, and a sequence of 12 amino acids containing the hypusine residue has been strictly conserved throughout eukaryotic evolution, from fungi to plants, insects, and mammals [3]. Hypusine formation, which has not been demonstrated in prokaryotes [2], is an absolute requirement for growth of $. cerevesiae [4], and a number of *Correspondin8 authors, Fax: (I) (212) 746 0300 and Fax: (I) (212) 746 6382, respectively.'For Stephen Biko (December 18, 1944.-September 12, 1977.reports have established correlations between hypusine formation and the proliferation of eukaryotic cells (see [2,3]). However, the exact physiological function of this presumed translation initiatic~n factor is unknown, and at present it even is unclear whether elF-SA functions at the pretranslational and/ or the translational level [3].Deoxyhypusyl hydroxylase (E.C. 1.14.99.29), which catalyses the final step of hypusine biosynthesis, is apparently related [5,6] to other protein hydroxy]ating enzymes such as prolyl 4-hydroxylase (E.C 1.14.11.2) [7] and is effectively inhibited by mimosine (3-(N-(3-hydroxypyridin-4-one))-2[S]-aminopropionic acid), both in vitro and in culture [3]. This coincides with proliferative arrest in the late GI phase ofthe cell cycle [3,[8][9][10][11]. Fast recovery ofcellular DOHH activity occurs upon mimo,,;ine removal, an effect parallele...

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Section: Resultssupporting

confidence: 72%

Detection of a sub‐set of polysomal mRNAs associated with modulation of hypusine formation at the G1‐S boundary Proposal of a role for eIF‐5A in onset of DNA replication

et al. 1995

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“…in gliricidia on cell division and DNA synthesis. The works of Tsai and Ling [16,17,18] have highlighted similar effects. There may have been the inhibition of the proliferation of spermatogenic cells within the epithelium of the seminiferous tubules, thus reducing spermatozoa production.…”

Section: Discussionmentioning

confidence: 52%

Effect of leucaena and gliricidia leaf meals on the seminal characteristics, testis weights and seminiferous tubule diameters of rabbits

2005

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-Eighteen crossbred rabbit bucks aged 8-10 months were placed on one of three diets containing leucaena (LLM), gliricidia (GLM) leaf meals both included at 20% of dry matter, or a control diet (CTL). Semen volume for the CTL group was 0.71 ± 0.02 mL, which was higher (P<0.05) than the values for the LLM (0.57 ± 0.02 mL) and GLM (0.58 ± 0.01 mL) groups. The spermatozoa concentration values obtained were (110.3 ± 3.5) × 10 6 per mL, (103.5 ± 4.1) × 10 6 per mL and (94.2 ± 3.4) × 10 6 per mL for the CTL, LLM and GLM groups respectively. Seminiferous tubular diameters were significantly (P<0.05) wider in the control group (234 ± 21.3 µm) than in the other two groups, which were similar (P>0.05). There were indications of mild degenerations in some samples from the leucaena and gliricidia groups. These results indicate that the inclusion of leucaena and gliricidia leaf meals at 20% in rations for mature rabbit bucks could cause mild depressive effects on semen production and quality. rabbit / semen / forage tree legume Résumé -Effet de l'incorporation de feuilles de leucaena ou de gliricidia dans l'alimentation des lapins sur les caractéristiques séminales, le poids des testicules et le diamètre des tubules séminifères. Dix-huit lapins mâles croisés âgés de 8 à 10 mois ont été répartis en trois groupes et ont reçu soit un régime supplémenté avec des feuilles de leucaena (LLM) ou de gliricidia (GLM) broyées, les deux incorporés à un taux de 20 % de matière sèche, soit un régime témoin (CTL). Le volume de sperme du groupe témoin a été de 0,71 ± 0,02 mL, volume plus élevé (P<0,05) que celui du groupe LLM (0,57 ± 0,02 mL) et du groupe GLM (0,58 ± 0,01 mL). La concentration en spermatozoïdes a été, respectivement, de (110,3 ± 3,5) × 10 6 par mL, (103,5 ± 4,1) × 10 6 par mL et (94,2 ± 3,4) × 10 6 par mL pour les groupes CTL, LLM et GLM. Le diamètre des tubules séminifères a été significativement plus élevé pour le groupe témoin (234 ± 21,3 µm) que pour les deux autres groupes, pour lesquels les diamètres ont été similaires (P>0,05). Des signes bénins de dégénérescence ont été observés dans quelques échantillons provenant des groupes LLM et GLM. Ces résultats suggèrent que l'incorporation de feuilles de leucaena ou de gliricidia à 20 % de matière sèche dans l'alimentation de lapins mâles adultes pourrait provoquer des effets délétères bénins sur la production et la qualité du sperme.lapin / sperme / fourrage de légumineuse arbustive

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“…The exceptions are DHP (compound 5) and mimosinamine (compound 8). Table 2 shows a comparison of the inhibitory effects of compounds 1, 5 and 8 on incorporation of [3H]thymidine into DNA in mouse bone marrow cells with those reported for H.Ep-2 cells (Tsai and Ling 1971) and sheep skin slices (Ward and Harris 1976). The discrepancies may be due to the use of different cell types as the test systems.…”

Section: Resultsmentioning

confidence: 99%

“…Ward and Harris (1976). B Data from Tsai and Ling (1971). c Tested at a concentration of 4 x 10-4 M.…”

Section: Resultsmentioning

confidence: 99%

Comparative Toxicities of Mimosine and Some Chemically Related Compounds to Mouse Bone Marrow Cells in Liquid Culture

Hegarty¹,

Lee²,

Christie³

et al. 1978

Aust. Jnl. Of Bio. Sci.

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Mimosine, a plant amino acid which is toxic in mammals, was shown to be a potent inhibitor of incorporation of [3H)thymidine in mouse bone marrow cells in liquid culture (> 70 % inhibition at a concentration of 2 x 10-4 M). To determine the parts of the molecule responsible for the inhibitory mechanism the effects of 13 chemically related compounds were examined in this system.The structural features necessary for inhibitory activity of the 4(IH)-pyridones were (1) the 3-hydroxyl-4-oxo function of the pyridone ring together with (2) an IX-alanine or a 2-aminoethyl side chain. Compounds based on several other hydroxy heterocyclic functions were either weakly active or inactive. 3-Hydroxy-4(IH)-pyridone, the goitrogen to which mimosine is converted in ruminants, was only slightly inhibitory. These results are compared with published information on the effects of some of these compounds on other types of mammalian cells in vitro.The mouse bone marrow system in which inhibition of incorporation of [3Hlthymidine is used as an index of cytotoxicity was shown to be sensitive and reproducible, and could be useful for structure-activity investigations of other cytotoxic compounds.

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Toxic action of mimosine—I. Inhibition of mitosis and DNA synthesis of H.Ep-2 cell by mimosine and 3,4-dihydroxypyridine

Cited by 40 publications

References 8 publications

Detection of a sub‐set of polysomal mRNAs associated with modulation of hypusine formation at the G1‐S boundary Proposal of a role for eIF‐5A in onset of DNA replication

Detection of a sub‐set of polysomal mRNAs associated with modulation of hypusine formation at the G1‐S boundary Proposal of a role for eIF‐5A in onset of DNA replication

Effect of leucaena and gliricidia leaf meals on the seminal characteristics, testis weights and seminiferous tubule diameters of rabbits

Comparative Toxicities of Mimosine and Some Chemically Related Compounds to Mouse Bone Marrow Cells in Liquid Culture

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