Study on expression of PS1 in APP-PS1 double gene stably transfected cell lines and its relation to gamma-secretase / 中华病理学杂志
Chinese Journal of Pathology
; (12): 297-301, 2005.
Article
em Zh
| WPRIM
| ID: wpr-265121
Biblioteca responsável:
WPRO
ABSTRACT
<p><b>OBJECTIVE</b>To study the role of presenilin1 (PS1) in the processing of beta-amyloid precursor protein (APP) to amyloid beta-peptide (Abeta) and its relation to gamma-secretase in the pathogenesis of Alzheimer's disease (AD).</p><p><b>METHODS</b>Several CHO cell lines stably transfected with either wide-type or mutant PS1 (M(146)L) along with APP(751) genes were established. The expression of PS1 and its half-life were determined by immunoprecipitation, Western blotting and pulse-chase experiment. Abeta released into the conditional media was quantitated by ELISA.</p><p><b>RESULTS</b>PS1 transfected CHO cells expressed an expected 45,000 full length protein. This over-expressed full length PS1 was subject to fast degradation with a half-life of less than 1 hour. In contrast to full length PS1, the truncated N-terminal and C-terminal proteins of PS1 were significantly more stable with a longer half-life of nearly 16 hours. Although the total amount of Abeta released into the conditional media did not show a significant difference between wild-type and mutant PS1 (M(146)L) transfected APP cells, mutant PS1 (M(146)L) transfected APP cells increase Abeta(1 - 42) (a subspecies of total Abeta) production with nearly a 2 fold increase, comparing to untransfected or wild-type PS1 transfected APP cells.</p><p><b>CONCLUSION</b>PS1 is involved in the processing of APP to Abeta, a nearly 2 fold increase of Abeta production in mutant PS1 (M(146)L) transfected APP cells indicates that PS1 may be the expected gamma-secretase itself.</p>
Texto completo:
1
Índice:
WPRIM
Assunto principal:
Fragmentos de Peptídeos
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Transfecção
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Peptídeos beta-Amiloides
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Cricetulus
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Células CHO
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Precursor de Proteína beta-Amiloide
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Secretases da Proteína Precursora do Amiloide
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Presenilina-1
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Doença de Alzheimer
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Genética
Limite:
Animals
Idioma:
Zh
Revista:
Chinese Journal of Pathology
Ano de publicação:
2005
Tipo de documento:
Article