ABSTRACT
Potential role of ERK1/2 kinase in conjunction with p38 in the regulation of inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) production, and superoxide anion generation by human neutrophils (PMNs) exposed to N-nitrosodimethylamine (NDMA) was determined. Increased synthesis of NO due to the involvement of iNOS in neutrophils exposed to NDMA was observed. In addition, intensified activation of ERK1/2 and p38 kinases was determined in these cells. Inhibition of kinase regulated by extracellular signals (ERK1/2) pathway, in contrast to p38 pathway, led to an increased production of NO and expression of iNOS in PMNs. Moreover, as a result of inhibition of ERK1/2 pathway, a decreased activation of p38 kinase was observed in neutrophils, while inhibition of p38 kinase did not affect activation of ERK1/2 pathway in these cells. An increased ability to release superoxide anion by the studied PMNs was observed, which decreased after ERK1/2 pathway inhibition. In conclusion, in human neutrophils, ERK1/2 kinase is not directly involved in the regulation of iNOS and NO production induced by NDMA; however, the kinase participates in superoxide anion production in these cells.
Subject(s)
Adolescent , Adult , Anions , Dimethylnitrosamine/pharmacology , Enzyme Inhibitors/pharmacology , Gene Expression Regulation, Enzymologic , Humans , Mitogen-Activated Protein Kinase 1/metabolism , Mitogen-Activated Protein Kinase 3/metabolism , Models, Biological , Neutrophils/metabolism , Nitric Oxide Synthase Type II/metabolism , Nitrites/chemistry , Oxygen/chemistry , Superoxides/metabolism , p38 Mitogen-Activated Protein Kinases/metabolismABSTRACT
Este tipo de estudio tiene especial interés para Chile dado el notable incremento de este cáncer, el cual se mantiene hasta la actualidad (1.628 muertes y tasa de 11,5 por 100.000 en 1995). La especie usada fue el hamster (Mesocricetus auratus) y un carcinógeno, la dimetil nitrosamina, fue administrado por vía oral, en una dosis establecida. Se formaron 3 grupos de 20 animales cada uno, por un tiempo que alcanza los seis meses. El primer grupo se organizó como control. El grupo control ha tenido muertes espontáneas después del primer año de vida y no ha mostrado ningún cáncer vesicular. Los otros dos grupos tienen muy poco tiempo de evolución para extraer conclusiones en relación a cáncer, pero habría un efecto protector de los antioxidantes