RESUMO
Inorganic arsenic is a major environmental contaminant associated with an increased risk of human skin cancer. Arsenic modulates cellular signaling pathways that affect diverse processes such as cell proliferation, differentiation, and apoptosis, including genotoxic damage. The p53 protein plays a central role in mediating stress and DNA damage responses, leading to either growth arrest or apoptosis. Several signal transduction pathways activated under a plethora of stressing conditions increase p53 protein levels. To further understand the molecular mechanisms involved in the arsenic mode of action, we explored the effects of this metalloid on the activation of the phosphatidyl inositol 3-kinase (PI3K)/Ca2+/diacylglicerol dependent protein kinase/protein kinase B (PKB) signaling cascade and its repercussion in p53 activation in two epithelial cell types: primary normal human keratinocytes cultures (NHK) and the carcinoma-derived C33-A cell line. Although in both cell systems arsenic leads to an increase in p53 and its binding to DNA, the final outcome is different. In NHK, arsenic triggers a sustained activation of the PI3K/PKB/glycogen synthase kinase-3 beta pathway, driving the cell into a cell-differentiated stage in which the proliferation signals are turned down. In sharp contrast, in C33-A cells, arsenic leads to a transient increase in p53 followed by a drastic reduction in its nuclear levels and an increase in cell proliferation. These findings favor the notion that p53-stage and transcriptional abilities are important to understand modifications in the proliferation-differentiation balance, an equilibrium that is severely impaired by arsenic.
Assuntos
Adenocarcinoma/tratamento farmacológico , Arsenitos/toxicidade , Poluentes Ambientais/toxicidade , Inibidores Enzimáticos/toxicidade , Células Epiteliais/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Compostos de Sódio/toxicidade , Proteína Supressora de Tumor p53/metabolismo , Adenocarcinoma/metabolismo , Núcleo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Citocalasina B/farmacologia , Dano ao DNA , Proteínas de Ligação a DNA , Relação Dose-Resposta a Droga , Combinação de Medicamentos , Células Epiteliais/metabolismo , Feminino , Células HeLa , Humanos , Recém-Nascido , Masculino , Micronúcleos com Defeito Cromossômico/induzido quimicamente , Transdução de Sinais , Proteína Supressora de Tumor p53/genética , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/metabolismoRESUMO
Al estudiar integralmente un grupo de 237 pacientes diabéticos del Policlínico Comunitario Docente "Pedro Borrás" de Pinar del Río, se insistió en las enfermedades del sistema cardiovascular que presentaban los mismos, tanto en el interrogatorio en el examen físico; se les realizó a estos pacientes el electrocardiograma y telecardiograma; se clasificaron con respecto a su control metabólico, al tiempo de evolución de la enfermedad, y a la edad de los mismos, y se analizaron las afecciones cardiovasculares encontradas según los grupos confeccionados. Según los resultados hallados se extrajeron conclusiones y recomendacicones que exponemos en el trabajo