Modulation of translation factor's gene expression by histone deacetylase inhibitors in breast cancer cells

The histone deacetylase inhibitors sodium butyrate (NaBu) and trichostatin A (TSA) exhibit anti-proliferative activity by causing cell cycle arrest and apoptosis. The mechanisms by which NaBu and TSA cause apoptosis and cell cycle arrest are not yet completely clarified, although these agents are known to modulate the expression of several genes including cell-cycle- and apoptosis-related genes. The enzymes involved in the process of translation have important roles in controlling cell growth and apoptosis, and several of these translation factors have been described as having a causal role in the development of cancer. The expression patterns of the translation mechanism, namely of the elongation factors eEF1A1 and eEF1A2, and of the termination factors eRF1 and eRF3, were studied in the breast cancer cell line MCF-7 by real-time quantitative reverse transcription-polymerase chain reaction after a 24-h treatment with NaBu and TSA. NaBu induced inhibition of translation factors' transcription, whereas TSA caused an increase in mRNA levels. Thus, these two agents may modulate the expression of translation factors through different pathways. We propose that the inhibition caused by NaBu may, in part, be responsible for the cell cycle arrest and apoptosis induced by this agent in MCF-7 cells.

Subunits of the chaperonin CCT are associated with Tetrahymena microtubule structures and are involved in cilia biogenesis

The cytosolic chaperonin CCT is a heterooligomeric complex of about 900 kDa that mediates the folding of cytoskeletal proteins. We observed by indirect immunofluorescence that the Tetrahymena TpCCTalpha, TpCCTdelta, TpCCTepsilon, and TpCCTeta-subunits colocalize with tubulin in cilia, basal bodies, oral apparatus, and contractile vacuole pores. TpCCT-subunits localization was affected during reciliation. These findings combined with atomic force microscopy measurements in reciliating cells indicate that these proteins play a role during cilia biogenesis related to microtubule nucleation, tubulin transport, and/or axoneme assembly. The TpCCT-subunits were also found to be associated with cortex and cytoplasmic microtubules suggesting that they can act as microtubule-associated proteins. The TpCCTdelta being the only subunit found associated with the macronuclear envelope indicates that it has functions outside of the 900 kDa complex. Tetrahymena cytoplasm contains granular/globular-structures of TpCCT-subunits in close association with microtubule arrays. Studies of reciliation and with cycloheximide suggest that these structures may be sites of translation and folding. Combined biochemical techniques revealed that reciliation affects the oligomeric state of TpCCT-subunits being tubulin preferentially associated with smaller CCT oligomeric species in early stages of reciliation. Collectively, these findings indicate that the oligomeric state of CCT-subunits reflects the translation capacity of the cell and microtubules integrity.

Impacto da síncope na qualidade de vida: validação duma escala de avaliação em doentes submetidos a teste de inclinação em mesa basculante

Introdução e objetivos: A síncope recorrente tem um impacto significativo na qualidade de vida. O desenvolvimento de escalas de medida de fácil aplicabilidade clínica para avaliar este impacto é fundamental. O objetivo do presente estudo é a validação preliminar da escala Impact of Syncope on Quality of Life, para a população portuguesa. Métodos: O instrumento foi submetido a um processo de tradução, validação, adequação cultural e cognitive debriefing. Participaram 39 doentes com história de síncopes recorrentes (>1 ano de evolução), submetidos a teste de inclinação em mesa basculante (teste de tilt), que constitui uma amostra de conveniência, com idade de 52,1±16,4 anos (21-83; 43,5% do sexo masculino), a maioria com uma situação profissional ativa (n=18) ou reformados (n=13). A versão portuguesa resultou numa versão semelhante unidimensional à original com 12 itens agregados num único somatório, tendo passado por validação estatística, com avaliação da fidelidade, validade e estabilidade no tempo. Resultados: Em relação à fidelidade, a consistência interna da escala é de 0,9. Avaliámos a validade convergente, tendo obtido resultados estatisticamente significativos (p<0,01). Avaliámos a validade divergente tendo obtido resultados estatisticamente significativos. Relativamente à estabilidade no tempo foi efetuado um teste-reteste do instrumento aos seis meses após o teste de inclinação com 22 doentes desta amostra não submetidos a intervenção clínica, que não mostrou alterações estatisticamente significativas da qualidade de vida. Conclusões: Os resultados obtidos indicam a pertinência da utilização deste instrumento em contexto português na avaliação da qualidade de vida de doentes com síncope recorrente.