RESUMO
The tumor suppressor protein p53 is implicated in cell cycle arrest and DNA repair as well as in apoptosis. In the CNS, p53 has been associated with neuronal cell death following various insults, including cerebral ischemia. We investigated the expression of p53 messenger RNA and protein, and the messenger RNA expression of the p53-responsive gene p21(WAF1/CiP1, in specific hippocampal regions following 15 min of normothermic and neuroprotective hypothermic (33 degrees C) global forebrain ischemia in the rat. Both p53 and p21WAF1/Cip1 messenger RNAs were transiently induced in ischemia resistant regions following normo- and hypothermic ischemia. In the ischemia sensitive CA1 region, p53 and p21WAF1/Cip1 messenger RNAs were up-regulated throughout reperfusion following the normothermic insult. The p53 protein levels increased following the insult, most markedly in ischemia-resistant CA3 neurons after normothermic ischemia, and in the CA1 neurons following hypothermic ischemia. Concomitantly, the protein was translocated to nuclei. These findings indicate that p53 and p21WAF1/Cip1 are not markers of neuronal death following global cerebral ischemia. Their rapid and transient induction correlates with cell survival, and suggests a possible role in DNA repair.
Assuntos
Ciclinas/genética , Expressão Gênica/fisiologia , Ataque Isquêmico Transitório/genética , Ataque Isquêmico Transitório/metabolismo , Neurônios/fisiologia , Proteína Supressora de Tumor p53/metabolismo , Animais , Biomarcadores , Northern Blotting , Morte Celular , Inibidor de Quinase Dependente de Ciclina p21 , DNA Complementar/genética , Imuno-Histoquímica , Ataque Isquêmico Transitório/patologia , Masculino , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Proteína Supressora de Tumor p53/genéticaRESUMO
Initially the data bank, which serves for the follow-up organization and for scientific studies, is briefly introduced. Then the possible analyses are described. Two types of possible evaluations can be distinguished. For the first type of evaluation, a subprogram has to be developed for every topic. A great number of questions can be answered by assembling the subprograms. These evaluations mostly dispose of a direct access to the data bank, so that the information desired is immediately available. For the second type of evaluation, the features of a group of patients have been determined with the aid of the data bank and have been stored then. A simple questioning language allows the establishment of any condition limiting the patient groups and its transmission to a statistical program package. Some examples are given to describe the possibilities of the statistical program developed especially for medical studies which makes it possible to perform analyses according to the life table method, too.
