Is melatonin a microtubule inhibitor?

The effect of melatonin (5-methoxy-N-acetyltryptamine) on microtubule assembly was assessed by means of viscometry, cell kinetics and [³H]colchicine binding studies. Evidence presented shows that melatonin has no effect on the in vitro assembly of bovine brain microtubules. [³H]Colchicine binding is not inhibited by melatonin in either crude or purified tubulin preparations. Furthermore, no increase in mitotic index is observed when Chinese hamster ovary cells are treated with melatonin; nor is neurite formation in neurobiastoma cells in culture affected by melatonin. It is concluded that melatonin does not interact with microtubules in a manner similar to colchicine and the Vinca alkaloids and it should not be classified as a colchicine-like mitotic inhibitor.     

Vesicular transport: how many Ypt/Rab-GTPases make a eukaryotic cell?

In eukaryotic cells, protein transport through the secretory and endocytic pathways is mediated by vesicular intermediates. Individual transport steps are regulated by Ras-like guanine nucleotide-binding proteins, termed Ypt in yeast or Rab in mammals. The complete sequencing of the Saccharomyces cerevisiae genome has revealed the total number of Ypt GTPases in this organism. There is some redundancy among the 11 Ypt proteins, and only those involved in the biosynthetic pathway are essential for celi viability.     

Peptide deformylase of eukaryotic protists: a target for new antiparasitic agents?

Peptide deformylase is found only in Eubacteria, making it a logical target for discovering new antibacterial agents. Although this protein is absent from animal or fungal cells, evidence supports its existence in eukaryotic protists, including the causative agents of malaria, sleeping sickness, Chagas disease and leishmaniosis. Here, Thierry Meinnel discusses the idea that deformylase inhibitors could be used as very broad-spectrum antibiotics against bacterial infections, as well as parasitic diseases.     

Is tyramine a specific inhibitor of proctolin?

Samples of tyramine purchased from six different manufacturers were tested for their effectiveness and specificity in blocking proctolin- and neurally-evoked contractions of the superior longitudinal muscles of the locust (Locusta migratoria) rectum. It was found that tyramine was neither specific (in that it also blocked glutamatergic responses) nor consistent in its action, as samples purchased from different manufacturers gave a range of different results. The venom of the wasp Philanthus triangulum was used to block glutamatergic responses to enable proctolinergic responses to be studied in isolation. Thin layer chromatography was performed to determine the purity of the tyramine samples but no correlation could be made between purity and efficacy or specificity of proctolinergic antagonism. It is concluded that, due to the inconsistency and non-specificity of its action, tyramine should not be used as an antagonist for proctolin.     

Tandem termination signals: myth or reality?

In two Escherichia coli genomes, laboratory strain K-12 and pathological strain O157:H7, tandem termination codons as a group are slightly over-represented as termination signals. Individually however, they span the range of representations, over, as expected, or under, in one or both of the strains. In vivo, tandem termination codons do not make more efficient signals. The second codon can act as a backstop where readthrough of the first has occurred, but not at the expected efficiency. UGAUGA remains an enigma, highly over-represented, but with the second UGA a relatively inefficient back up stop codon.     

Protease inhibitor frequencies: is there a deficit of M subtype heterozygotes?

A large number of reports on human protease inhibitor (PI) type frequencies in various populations have now appeared. A combination of the results of published studies shows that the observed frequencies of the M subtype homozygotes and heterozygotes differ significantly from those predicted by the Hardy-Weinberg equilibrium, especially among Europeans but probably not among Asians or Africans. The M1, M2 and M3 homozygotes are more numerous than would be expected, while the M1M2 and M1M3 heterozygotes are less common than expected.     

Initiation of eukaryotic DNA replication: conservative or liberal?

The mechanism for initiation of eukaryotic DNA replication is highly conserved: the proteins required to initiate replication, the sequence of events leading to initiation, and the regulation of initiation are remarkably similar throughout the eukaryotic kingdom. Nevertheless, there is a liberal attitude when it comes to selecting initiation sites. Differences appear to exist in the composition of replication origins and in the way proteins recognize these origins. In fact, some multicellular eukaryotes (the metazoans) can change the number and locations of initiation sites during animal development, revealing that selection of initiation sites depends on epigenetic as well as genetic parameters. Here we have attempted to summarize our understanding of this process, to identify the similarities and differences between single cell and multicellular eukaryotes, and to examine the extent to which origin recognition proteins and replication origins have been conserved among eukaryotes. Published 2000 Wiley-Liss, Inc.     

Is IL-2 regulated by a serum inhibitor?

Normal murine serum inhibits the proliferation of cloned cytotoxic T lymphocytes driven by pure interleukin 2 (IL-2), indicating that a component of normal murine serum is directly inhibitory to IL-2-dependent proliferation. However, the effect is not specific to such cells, since an IL-2-independent variant cell, and a number of lymphoid tumor cell lines are similarly inhibited. Addition of purified IL-2 does not overcome the inhibition, although its degree is reduced. Fractionation of murine serum showed that there are at least two inhibitory activities, which migrate with globular proteins of molecular weights greater than or equal to 10(6) and 4 X 10(4), respectively, on gel chromatography. Neither of the activities was specific for IL-2-dependent cells. Furthermore, murine IL-2 is stable in murine serum in vitro, although it disappears rapidly from the circulation after intravenous injection. It is therefore unlikely that serum inhibitor of IL-2 is an important immunoregulator in vivo.     

Silibinin: a novel inhibitor of Aβ aggregation

Alzheimer's disease (AD) is characterized by the abnormal aggregation of amyloid β peptide (Aβ) into extracellular fibrillar deposits known as amyloid plaque. Inhibition of Aβ aggregation is therefore viewed as a potential method to halt or slow the progression of AD. It is reported that silibinin (silybin), a flavonoid derived from the herb milk thistle (Silybum marianum), attenuates cognitive deficits induced by Aβ25-35 peptide and methamphetamine. However, it remains unclear whether silibinin interacts with Aβ peptide directly and decreases Aβ peptide-induced neurotoxicity. In the present study, we identified, through employing a ThT assay and electron microscopic imaging that silibinin also appears to act as a novel inhibitor of Aβ aggregation and this effect showed dose-dependency. We also show that silibinin prevented SH-SY5Y cells from injuries caused by Aβ(1-42)-induced oxidative stress by decreasing H(2)O(2) production in Aβ(1-42)-stressed neurons. Taken together, these results indicate that silibinin may be a novel therapeutic agent for the treatment of AD.