The Change of Expression in Amyloid Precursor Protein mRNA and Amyloid Precursor Protein by Transient Ischemia

ABSTRACT

Although the mechanism has not been clearly understood, it has been reported that various altered gene expressions are induced by cerebral ischemia. In order to investigate the effects of transient cerebral ischemia on the amyloid precursor protein(APP) metabolism, the 3 isoforms of APP mRNA and the APP were examined. Rats were given ischemic insult through middle cerebral artery occlusion and reperfusions using blunted 4-0 nylon thread after exposure of cervical region. Groups were assigned with each being 1 hour occlusion and 1hr, 3hrs, 8hrs, 1day, 3days, 7days after reperfusion. The rats were then sacrificed and cerebral cortex of each animal was dissected. The mRNA level of APP770, 751, 695 was investigated by reverse transcription coupled polymerase chain reaction (RT-PCR) and the protein amount of APP was investigated by Western blotting method. The results showed that transient ischemia induced the change of APP mRNA. The APP mRNA which encodes the KPI(Kunitz-type protease inhibitor) domain began to increase after 1 day, reaching a maximun at 3 days, and then decreased to control level in the 7 days. The protein level of APP was same until 7 days. We conclude that transient cerebral ischemia alters the gene expression of APP isoforms. Therefore, we speculate that some factors regulating the splicing of APP gene transcript may also undergo ischemia-induced changes and the increase in levels of KPI-APP following ischemia might be associated with pathological changes during the ischemic process.