The tumor suppressor p53 and its response gene p21(WAF1/Cip1) are not markers of neuronal death following transient global cerebral ischemia
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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°C) global forebrain ischemia in the rat. Both p53 and p21(WAF1/Cip1) messenger RNAs were transiently induced in ischemia resistant regions following normo- and hypothermic ischemia. In the ischemia sensitive CA1 region, p53 and p21(WAF1/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 p21(WAF1/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.