RESUMO
The gene p8 encodes for a small cytoprotective protein with no apparent enzymatic activity being proposed to act as co-transcription factor whose expression is increased during inflammation. Recent data from astrocytes demonstrates that p8 suppression leads to induction of heme oxygenase 1 (HO-1). Here, we assessed the cross-talk between p8 and HO-1 in mouse embryonic fibroblasts (MEF) observing an increased expression of HO-1 in p8-deficient (p8(-/-)) MEFs in non-treated and treated conditions. This effect was independent of the cell cycle. Our findings revealed that generation of reactive oxygen species (ROS) was higher in p8(-/-) MEFs. Mitochondria and NADPH oxidases were not the origin of ROS. This observation was not restricted to MEF as suppression of p8 gene transcription in MiaPaCa-2 cells also led to increased intracellular ROS. Additionally, p8 deficiency did not affect the Rac1 dependant NADPH oxidase complex. Our data shows that p8 deficiency increases ROS and subsequently the expression of anti-oxidative enzymes, such as HO-1, suggesting an involvement in the anti-oxidative defense. Moreover, we suggest that the severity of AP observed in p8(-/-) mice is induced by an impaired anti oxidative capacity of the pancreas, which is caused by increased generation of ROS.
Assuntos
Proteínas de Ligação a DNA/deficiência , Embrião de Mamíferos/metabolismo , Fibroblastos/metabolismo , Heme Oxigenase-1/metabolismo , Proteínas de Membrana/metabolismo , Mitocôndrias/metabolismo , Proteínas de Neoplasias/deficiência , Espécies Reativas de Oxigênio/metabolismo , Animais , Linhagem Celular , Embrião de Mamíferos/patologia , Fibroblastos/patologia , Heme Oxigenase-1/genética , Proteínas de Membrana/genética , Camundongos , Camundongos Knockout , Mitocôndrias/patologia , Pâncreas/metabolismo , Pâncreas/patologia , Transcrição Gênica/genéticaRESUMO
Invasive liver abscess syndrome (ILAS) is caused by strains of hypervirulent Klebsiella pneumoniae (hvKp) and has emerged as the leading cause of liver abscesses in immuno-competent patients (L.K. Siu et al. Lancet Infect Dis 2012; 12: 881-87). ILAS is frequently associated with metastatic spread including the eyes, lungs, and the central nervous system. The morbidity and mortality of affected patients are increased compared to liver abscesses of other origin, especially in cases with concomitant diabetes mellitus (J. E. Choby et al. J Intern Med 2020; 287(3): 283-300). Immediate diagnosis and early intervention are essential for an optimal outcome. Therefore, ultrasound plays a crucial role if hvKp is suspected. However, experience with the characteristics of such abscesses on contrast-enhanced ultrasound (CEUS) is very limited.