RESUMO
A new synthetic drug, benzamide riboside (BR) exhibited strong oncolytic activity against leukemic cells in the 5-10 microM range. Higher BR-concentrations (20 microM) predominantly induced necrosis which correlated with DNA strand breaks and subsequent depletion of ATP- and dATP levels. Replenishment of the ATP pool by addition of adenosine prevented necrosis and favoured apoptosis. This effect was not a pecularity of BR-treatment, but was reproduced with high concentrations of all trans-retinoic acid (120 microM) and cyanide (20 mM). Glucose was also capable to suppress necrosis and to favour apoptosis of HL-60 cells, which had been treated with necrotic doses of BR and cyanide. Apoptosis eliminates unwanted cells without affecting the microenvironment, whereas necrosis causes severe inflammation of surrounding tissues due to spillage of cell fluids into the peri-cellular space. Thus, the monitoring and maintenance of cellular energy pools during therapeutic drug treatment may help to minimize nonspecific side effects and to improve attempted drug effects.
Assuntos
Trifosfato de Adenosina/fisiologia , Antineoplásicos/toxicidade , Apoptose , Necrose , Nucleosídeos/toxicidade , Adenosina/farmacologia , Trifosfato de Adenosina/análise , Benzamidas/farmacologia , Ensaio Cometa , Dano ao DNA , Nucleotídeos de Desoxiadenina/análise , Nucleotídeos de Desoxicitosina/análise , Desoxirribonucleotídeos/análise , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/farmacologia , Células HL-60 , Humanos , IMP Desidrogenase/antagonistas & inibidores , Inibidores de Poli(ADP-Ribose) Polimerases , Cianeto de Potássio/antagonistas & inibidores , Tretinoína/antagonistas & inibidoresRESUMO
Vimentin contributes to the cytoskeleton of different cell-types, among them glial cells. We report here that different forms of this protein, distinguishable by the monoclonal antibodies Vim3B4 and V9, are species-specifically expressed in cultures of glial fibrillary acidic protein (GFAP) positive, primary astrocytes of the chicken and rat. Most cells in the cultures co-expressed GFAP and one of the two vimentin epitopes. The Vim3B4 positive epitope was present in chicken astrocytes, while the V9 positive was not. Inverse situation was found in the astrocytes of rat. In vitro age of the cells did not influence the hierarchy of vimentin epitope expression with respect to species-specificity. Our result shows that the different vimentin expression program of cultured astrocytes of the chicken and rat is preserved under in vitro conditions. The presented data support the concept of the species-specific regulation of vimentin forms in glial cells of the central nervous system.
