RESUMO
No abstract available.
RESUMO
Reactive oxygen species (ROS) contribute to the development of a number of neuronal diseases including ischemia. DJ-1, also known to PARK7, plays an important role in transcriptional regulation, acting as molecular chaperone and antioxidant. In the present study, we investigated whether DJ-1 protein shows a protective effect against oxidative stress-induced neuronal cell death in vitro and in ischemic animal models in vivo. To explore DJ-1 protein's potential role in protecting against ischemic cell death, we constructed cell permeable Tat-DJ-1 fusion proteins. Tat-DJ-1 protein efficiently transduced into neuronal cells in a dose- and time-dependent manner. Transduced Tat-DJ-1 protein increased cell survival against hydrogen peroxide (H2O2) toxicity and also reduced intracellular ROS. In addition, Tat-DJ-1 protein inhibited DNA fragmentation induced by H2O2. Furthermore, in animal models, immunohistochemical analysis revealed that Tat-DJ-1 protein prevented neuronal cell death induced by transient forebrain ischemia in the CA1 region of the hippocampus. These results demonstrate that transduced Tat-DJ-1 protein protects against cell death in vitro and in vivo, suggesting that the transduction of Tat-DJ-1 may be useful as a therapeutic agent for ischemic injuries related to oxidative stress.
Assuntos
Animais , Camundongos , Ratos , Barreira Hematoencefálica/metabolismo , Isquemia Encefálica/metabolismo , Região CA1 Hipocampal/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Gerbillinae , Peptídeos e Proteínas de Sinalização Intracelular/administração & dosagem , Peroxidação de Lipídeos , Malondialdeído/metabolismo , Fármacos Neuroprotetores/administração & dosagem , Proteínas Oncogênicas/administração & dosagem , Estresse Oxidativo , Prosencéfalo/efeitos dos fármacos , Proteínas Recombinantes de Fusão/administração & dosagem , Produtos do Gene tat do Vírus da Imunodeficiência Humana/administração & dosagemRESUMO
The purpose of this paper is to provide reference data related to the body weight, food & water consumptions, urinalysis, hematology and serum biochemistry parameters and absolute & relative organ weights obtained from control Sprague-Dawley rats, used in the 4-week and 13-week repeated-dose toxicity studies conducted in our laboratory between 2005 and 2008. The mean, standard deviation, minimum and maximum range values for hematology and serum biochemistry parameters, data of absolute & relative organ weights, and the difference between sexes and study duration of week 4 versus 13 week are presented. The studies were conducted according to "the standards of Toxicity Study for Medicinal Products" (2005) and The KFDA Notification No. 2000-63 'Good Laboratory Practice (GLP)' (2000) issued by KFDA. These data could be used as reference material of Sprague-Dawley rats by conducting the studies to evaluate the toxicological profile of pre-clinical toxicity studies.