Mimosine

In the present paper, tyrosinase inhibition studies and structure–activity relationship of eight cycloartane glycosides and one cucurbitane glycoside and its genin, which were isolated from Astragalus (Leguminoseae) and Bryonia (Cucurbitaceae) plants, have been discussed. The activities are compared with two reference tyrosinase inhibitors, kojic acid and l-mimosine. These studies and the SAR showed that the askendoside B which exhibited highly potent (IC50 = 13.95 μM) tyrosinase inhibition could be a possible lead molecule for the development of new medications of several skin diseases related with the over-expression of the enzyme tyrosinase, like hyperpigmentation. The molecule also may be interesting for the cosmetic industries as a skin whitening agent.

This paper reports the effect of the tyrosinase (monophenol o-diphenol:oxygen oxidoreductase; EC 1.14.18.1) inhibitors diethyldithiocarbamate (DETC), L-tropolone, kojic acid, phenylthiourea (PTU) and L-mimosine on the in vitro growth of Tuber borchii (a white truffle) mycelium. A significant inhibitory effect on mycelium growth was observed for DETC, PTU and L-tropolone (0% growth compared to control at 100 μg ml−1 DETC, PTU and L-tropolone and at 10 μg ml−1 DETC and L-tropolone). As a comparison the action of the same inhibitors was also tested on the growth and pigmentation of the mould Cladosporium sphaerospermum. In the presence of CuSO4 10−6 M T. borchii mycelium acquired pigmentation (as rounded aggregates compared to control revealed by SEM microscopy). Tyrosinase activity in the extract from T. borchii mycelium (18-day culture) was detected spectrophotometrically.

The effects of three compounds on the cell cycle of HL-60 promyeloid leukemia cells has been examined. Ciclopirox olamine, an antifungal agent, and the compound Hoechst 768159 reversibly block the cell cycle at a point occurring roughly 1 h before the arrest mediated by aphidicolin, an inhibitor of DNA polymerase á activity, which acts in early S phase. Similar results are also obtained with the compound mimosine, a plant amino acid. Based on these data, it is concluded that all three agents inhibit cell cycle traverse at or very near the G1/S phase boundary and identify a previously undefined reversible cell cycle arrest point.

The legume Leucaena leucocephala (Leucaena) is widely used to supplement forage in silvopastoral livestock systems in Latin America. Little is known about its possible effects on the cow reproductive dynamic. The aim was to evaluate the effect of Leucaena foliage intake on re-establishment of ovarian activity and estrus behavior in early postpartum (7-90 days) cows. Twenty-four multiparous Bos taurus × Bos indicus cows were divided into two homogenous groups and assigned to one of two treatments: a silvopastoral system (SS, n = 12), consisting of an association of Cynodon nlemfuensis grass and L. leucocephala; and a control system (CS, n = 12), consisting of C. nlemfuensis alone. Intake of Leucaena in the SS ranged from 3.80 to 6.43 kg DM/cow/day. Plasma mimosine concentrations ranged from 1270 to 1530 μg/mL, and those for 2,3-dihydroxypyridine (DHP) from 147 to 729 μg/mL. No 3,4-DHP was detected in plasma. No difference (P > 0.05) between treatments was observed for the number of cows exhibiting small, medium, or dominant follicles, or estrus behavior. The number of cows which re-established ovarian cyclicity (n = 6) was lower (P < 0.05) in the SS than in the CS (n = 9). Corpus luteum lifespan was longer (P < 0.05) in the SS than in the CS. Intake of Leucaena affected the number of cows exhibiting ovarian cyclicity and extended corpus luteum life, but did not affect follicular development and estrus behavior.

Previous studies on the cell cycle of Arabidopsis thaliana have been hindered by the lack of synchronous cell culture systems. We have used liquid callus cultures and a cycloheximide-synchronized suspension culture of Arabidopsis to investigate changes in cyclin transcript levels in response to exogenous auxin, cytokinin, and nutrients, and during the cell cycle. CYCD1 ([delta]1) transcript was virtually undetectable in liquid-cultured callus or suspension-culture cells. CYCD2 ([delta]2) transcript levels were largely unaffected by the readdition of phytohormones or nitrate to the growth medium, and remained constant throughout the cell cycle in suspension-culture cells. CYCD3 ([delta]3) transcript levels were strongly dependent on nitrate, and were induced at the G1/S transition following phytohormone readdition. In synchronized suspension-culture cells, CYCD3 transcript accumulated during the S phase, and remained constant thereafter. These results support the hypothesis that D cy...

Previous radiolabeling and two-dimensional (2-D) gel studies of the dihydrofolate reductase (DHFR) domain of Chinese hamster cells have suggested that replication can initiate at any one of a very large number of inefficient sites scattered throughout the 55-kb intergenic spacer region, with two broad subregions (ori-β and ori-γ) preferred. However, high-resolution analysis by a PCR-based nascent strand abundance assay of the 12-kb subregion encompassing ori-β has suggested the presence of a relatively small number of fixed, highly efficient initiation sites distributed at infrequent intervals that correspond to genetic replicators. To attempt to reconcile these observations, two different approaches were taken in the present study. In the first, neutral-neutral 2-D gel analysis was used to examine replication intermediates in 31 adjacent and overlapping restriction fragments in the spacer, ranging in size from 1.0 to 18 kb. Thirty of 31 fragments displayed the complete bubble arcs ...

To analyze relationships between replication and homologous recombination in mammalian cells, we used replication inhibitors to treat mouse and hamster cell lines containing tandem repeat recombination substrates. In the first step, few double-strand breaks (DSBs) are produced, recombination is slightly increased, but cell lines defective in non-homologous end-joining (NHEJ) affected in ku86 (xrs6) or xrcc4 (XR-1) genes show enhanced sensitivity to replication inhibitors. In the second step, replication inhibition leads to coordinated kinetics of DSB accumulation, Rad51 foci formation and RAD51-dependent gene conversion stimulation. In xrs6 as well as XR-1 cell lines, Rad51 foci accumulate more rapidly compared with their respective controls. We propose that replication inhibition produces DSBs, which are first processed by the NHEJ; then, following DSB accumulation, RAD51 recombination can act.

Cell cycle control, faithful DNA replication, repair and recombination are associated in a network of pathways controlling genome maintenance. In mammalian cells, inhibition of replication produces DNA breaks and induces RAD51-dependent recombination, in a late step. Here we examine whether the status of p53 affects this process in mouse L-cells containing a recombination substrate. We show that expression of the mutant (His175)p53 strongly stimulates recombination induced by aphidicolin, in a late step (kinetically related to the RAD51 step). Mutant p53 stimulates recombination induced by the replication elongation inhibitors (aphidicolin, hydroxyurea and Ara-C) but is without effect on recombination induced by the initiation inhibitors (mimosine and ciclopirox olamine). We compared the impact of several p53 mutations showing different effects on the G1 checkpoint and on recombination. We show that the mutant (Pro273)p53 protein, which does not alter the G1 checkpoint, strongly stimulates recombination induced by elongation inhibitors. These results show that p53 can act on recombination induced by replication arrest independently of its role in the G1 checkpoint. An action of p53 via the RAD51 pathway is discussed.