Prion protein (PrP C ), when associated with the secreted form of the stress-inducible protein 1 (STI1), plays an important role in neural survival, neuritogenesis, and memory formation. However, the role of the PrP C -STI1 complex in the physiology of neural progenitor/stem cells is unknown. In this article, we observed that neurospheres cultured from fetal forebrain of wild-type (Prnp 1/1 ) and PrP C -null (Prnp 0/0 ) mice were maintained for several passages without the loss of self-renewal or multipotentiality, as assessed by their continued capacity to generate neurons, astrocytes, and oligodendrocytes. The homogeneous expression and colocalization of STI1 and PrP C suggest that they may associate and function as a complex in neurosphere-derived stem cells. The formation of neurospheres from Prnp 0/0 mice was reduced significantly when compared with their wild-type counterparts. In addition, blockade of secreted STI1, and its cell surface ligand, PrP C , with specific antibodies, impaired Prnp 1/1 neurosphere formation without further impairing the formation of Prnp 0/0 neurospheres. Alternatively, neurosphere formation was enhanced by recombinant STI1 application in cells expressing PrP C but not in cells from Prnp 0/0 mice. The STI1-PrP C interaction was able to stimulate cell proliferation in the neurosphere-forming assay, while no effect on cell survival or the expression of neural markers was observed. These data suggest that the STI1-PrP C complex may play a critical role in neural progenitor/stem cells self-renewal via the modulation of cell proliferation, leading to the control of the stemness capacity of these cells during nervous system development.
Este artigo descreve a síntese e a caracterização de três novos complexos de platina(II) com a oxitetraciclina, doxiciclina e clortetraciclina por análise elementar, espectroscopias IV e RMN de II ions as a function of the pH were studied by 1 H NMR. All the investigated tetracyclines form 1:1 complexes with Pt II via the oxygen of the hydroxyl group and oxygen of the amide group at ring A. The minimal inhibitory concentrations (MIC) of the ligands and those of their Pt II compounds were determined in two sensitive strains (E. coli HB 101 and E. coli ATCC 25922) and in a resistant one (E. coli HB101/ pBR322). Platinum complex of doxycycline is twice as potent as the free antibiotic in the resistant strain. Octanol/water partition coefficients of the complexes were determined. Increasing lipophilicity enhances antimicrobial activity in the resistant strain.
We studied the cytotoxic effect and the uptake of Pd(II) complexes of doxycycline (Dox), [Pd(Dox)Cl2], and tetracycline (Tc), [Pd(Tc)Cl2], in chronic myelogenous leukemia cells. The effect of the compounds on macrophage viability was also investigated. Compound 1 is more effective than compound 2 in inhibiting the growth of K562 cells with the IC(50) values of 14.44 and 34.54 microM, respectively. There is a good correlation between cell-growth inhibition and intracellular metal concentrations, determined by inductively coupled plasma atomic emission spectroscopy (ICP-AES). Incubation of the cells with equitoxic concentrations of both compounds yields approximately the same intracellular Pd concentration. At the IC(50) doses, intracellular concentration is ca. 33 x 10(-16) mol/cell for both compounds 1 and 2. This suggests that more [Pd(Tc)Cl2] is needed to produce a cytotoxic effect, because it enters cells more slowly. Both compounds up to 16 microM did not affect the viability of mouse peritoneal macrophages after a 48-h incubation. After 72 h of incubation, the IC(50) values are 22 for [Pd(Dox)Cl2] and 40 microM for [Pd(Tc)Cl(2)]. Therefore, the cytotoxic effect in cancer cells exhibited by both compounds is higher than their effect in macrophages.
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