RESUMO
We examined the effect of trimidox-induced apoptosis involvement of p53 in the NALM-6 cell line of acute lymphoblastic leukemia. Trimidox has been shown to increase the induction of p53. Phosphorylation of p53 protein at Ser-15 and Ser-20 residues was activated earlier than the obvious increase in p53 expression. Pifithrin-alpha, a p53 inhibitor, significantly prevented trimidox-induced apoptotic characteristics, as detected by nuclear morphological observation and DNA fragmentation. Trimidox-induced apoptosis was enhanced or attenuated by transfection with wild-type or dominant-negative p53 containing expression vectors, respectively. These results indicate that one of the induction mechanisms of apoptosis by trimidox is the mediated augmentation of p53.
Assuntos
Apoptose/efeitos dos fármacos , Benzamidinas/farmacologia , Inibidores Enzimáticos/farmacologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Ribonucleotídeo Redutases/antagonistas & inibidores , Proteína Supressora de Tumor p53/fisiologia , Linhagem Celular Tumoral , Fragmentação do DNA , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Transdução de SinaisRESUMO
We examined the effect of trimidox (3,4,5-trihydroxybenzamidoxime) on the production of nitric oxide (NO) by lipopolysaccharide (LPS) in mouse RAW 264.7 macrophages. Trimidox (50 - 300 microM) concentration-dependently inhibited NO production by LPS (0.01, 0.1, or 1 microg/ml) after incubation for 24 h. LPS-induced expression of inducible NO synthase (iNOS) and degradation of IkappaBalpha were prevented by trimidox. The protective effect against NO production by LPS was not only observed in prior incubation but also later incubation with trimidox until iNOS was activated by LPS. These results suggest that trimidox has a predominantly protective effect against LPS-induced production of NO via iNOS expression.
