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ÀÏ°ý¼º ³úÇãÇ÷ÈÄ Amyloid Precursor Protein mRNA¿Í Amyloid Precursor Protein ¹ßÇöÀÇ º¯È­ The Change of Expression in Amyloid Precursor Protein mRNA and Amyloid Precursor Protein by Transient Ischemia

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ÀÌ»óÇü/Sang Hyung Lee ±èÇý¼±/Á¤¼ºÁø/ÀÌ¿µÀç/¼­À¯Çå/¾çÈñÁø/Á¤¿µ¼·/ÇÑ´ëÈñ/Á¶º´±Ô/Hye Sun Kim/Sung Jin Jeong/Young-Jae Lee/Yoo Hun Suh/Hee Jin Yang/Young Seob Jung/Dar Hee Han/Byung-Kyu Cho

Abstract

°á ·Ð
º» ¿¬±¸ÀÇ °á°ú´Â 1½Ã°£ÀÇ Áß´ë³úµ¿¸ÆÀÇ Æó»ö ÈÄ Àç°ü·ù½ÃÄ×À»¶§ ¹é¼­ÀÇ ´ë³úÇÇÁú¿¡¼­
APPmRNAÀÇ ÁÖµÈ 3 À̼ºÇüÀÎ APP770. APP751, APP695ÀÇ mRNAÀÇ º¯È­°¡ À¯µµµÇ¾ú´Ù.
ù°, APP751 ¹× APP770ÀÇ mRNA´Â 1ÀÏ ÀÌÈÄ¿¡ Áõ°¡Çϱ⠽ÃÀÛÇÏ¿© 3ÀÏ° ÃÖ°í ¼öÁØÀ¸·Î
Áõ°¡ÇÏ¿´À¸¸ç, 7ÀÏ°¿¡´Â ´Ù½Ã Àç°ü·ùÇϱâ ÀüÀ¸·Î °¨¼ÒÇÏ¿´´Ù. APP770ÀÇ mRNAÀÇ Áõ°¡´Â
1ÀÏ°¿¡´Â ¼ö¼úÇϱâ Àü°ú ´Ü¼øÈ÷ Æó»ö½ÃŲ °Í°ú ºñ±³ÇÒ ¶§ Áõ°¡ÀÇ Â÷ÀÌ°¡ ÀÖ¾úÀ¸¸ç(p<0.01),
3ÀÏ°¿¡´Â APP770 ¹× APP751ÀÇ myNAÀÇ Áõ°¡°¡ ¸ðµÎ Åë°èÀûÀ¸·Î À¯ÀÇÇÏ¿´´Ù(p<0.01). µÑ
°, APP695ÀÇmRNA´Â 1ÀÏ, 3ÀÏ°¿¡´Â °¨¼ÒÇÏ´Â °ÍÀ¸·Î º¸¿´À¸¸ç ¼ö¼ú Çϱâ Àü°ú ºñ±³ÇÒ
¶§ 3ÀÏ°¿¡´Â À¯ÀÇÇÑ °¨¼Ò°¡ ÀÖ¾ú´Ù(p<0.05).
ÀÏ°ú¼º ³úÇãÇ÷·Î ´ë³úÇÇÁú¿¡¼­ÀÇ APP´Â Àç°ü·ùÈÄ 7ÀϱîÁö º¯È­°¡ ¾ø´Â °ÍÀ¸·Î ³ªÅ¸³µ´Ù.
µû¶ó¼­ APP´Â KPI-APP°¡ ¸¹ÀÌ »ý°åÀ» °ÍÀ̹ǷΠ¾ÆÁ÷ ±× »ý¸®ÀûÀÎ ±â´ÉÀº Á¤È®È÷ ¾ËÁö ¸ø
ÇÏÁö¸¸ ÇãÇ÷ ÈÄ ´ë»ç¿¡ KPI-APF°¡ ¿µÇâÀ» ¹ÌÄ¥ °ÍÀ¸·Î »ý°¢µÇ¹Ç·Î ±× ¿ªÇÒ¿¡ ´ëÇÏ¿© ´õ
¸¹Àº ¿¬±¸°¡ ÇÊ¿äÇÒ °ÍÀ¸·Î »ý°¢µÇ¾ú´Ù.
#ÃÊ·Ï#
Although the mechanism has not been clearly understood, it has been reported that
various altered gene expressions are induced by cerebral ischmia. 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 inchemic insult through middle cerebral artery occlusion and
reperfusions using blunted 4-0 nylon thread after exposure of cervical region. Group
were assigned with each being 1 hour occlusion and 1hr, 2hrs, 8hrs, 1 day, 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 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.

Transient cerebral ischemia; Middle cerebral artery; APP(amyoid precursor protein); KPI(Kunitz-Type protease inhibitor);

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