RESUMO
Stress induces structural plasticity in neurons of the adult central nervous system (CNS) and alters the levels of cellular production of reactive oxygen species (ROS), and these changes might involve modifications of the antioxidant defense system. This study investigated whether acute stress altered the expression pattern of peroxiredoxin (Prx) III, which is an antioxidant enzyme that controls cytokine-induced peroxide levels. Prx III immunoreactivity was upregulated in the pyramidal neurons of the hippocampus and in the motor neurons of the spinal cord in an acute immobilization stress (AIS) model. In addition, we tested whether the transcription factor Foxo3a was necessary for the expression of Prx III. The depletion of Foxo3a led to a marked reduction of Prx III and a compensatory enhancement of mitochondrial superoxide dismutase (Mn-SOD) in PC12 cells. The results of this study suggest that Foxo3a mediates the neuronal levels of expression of Prx III and the levels of expression of Mn-SOD in mitochondria. These mechanisms may play an important role in neuroprotection against oxidative stress. Furthermore, Prx III upregulation might be an useful approach for the management of stress.
Assuntos
Fatores de Transcrição Forkhead/metabolismo , Hipocampo/enzimologia , Imobilização/fisiologia , Imobilização/psicologia , Peroxirredoxina III/metabolismo , Estresse Psicológico/metabolismo , Animais , Proteína Forkhead Box O3 , Fatores de Transcrição Forkhead/genética , Hipocampo/citologia , Humanos , Masculino , Mitocôndrias/enzimologia , Células PC12 , Peroxirredoxina III/genética , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Ratos , Ratos Sprague-Dawley , Medula Espinal/citologia , Medula Espinal/enzimologia , Superóxido Dismutase/metabolismo , Regulação para CimaRESUMO
Vitamin D3 upregulated protein 1 (VDUP1) is a stress-response gene that is upregulated by 1,25(OH)2D3 in tumor cells. The in vivo roles of VDUP1 were investigated by producing mice lacking VDUP1 (VDUP1-/- mice). VDUP1-/- mice showed minimal changes in the development of T and B cells, but there was a profound reduction in the numbers of natural killer (NK) cells. As well, these mice showed decreased NK activity. In the VDUP1-/- mice, the expression of CD122 was reduced, demonstrating that VDUP1 is required for CD122 expression and NK maturation. In addition, severe lymphoid hyperplasia in the small intestine was observed in VDUP1-/- mice. Taken together, these results suggest that VDUP1 is a critical factor for the development and function of NK cells in vivo.