[Influence of APP(SWE) transfection on nicotinic receptors in cultured neuronal cells].
OBJECTIVE
To investigate the influence of APP(SWE) on the expression of neuronal acetylcholine receptors (nAChRs) and its relationship with Alzheimer's disease (AD).


METHODS
APP(SWE), carried the Swedish family AD double mutants, were transfected into SH-SY5Y cells and primary cultured neurons from rat brains to build a cellular model of AD. The mRNA levels of APP and nAChRs, and the protein levels of total APP, αAPPs and nAChRs in the cultured cells were measured using real-time PCR and Western blot, respectively. The numbers of α3 nAChR were determined by receptor-[³H]epibatidine binding assay.


RESULTS
Increased expressions of Swedish 670/671 APP at mRNA and protein levels, and down-regulation of αAPPs were observed in both of the cultured neuronal cells transfected with APP(SWE). A significant increase of α7 nAChR expression at protein and mRNA levels was detected in the APP(SWE) transfected SH-SY5Y cells. On the other hand, after transfection with APP(SWE), the expressions of α3 nAChR at protein and mRNA levels in SH-SY5Y cells, and α4 nAChR at mRNA level in primary cultured neurons were inhibited. In addition, the numbers of receptor binding sites were deceased in SH-SY5Y cells overexpressing with APP(SWE).


CONCLUSIONS
Overexpression of APP(SWE) can decrease αAPPs and modify nAChRs by increasing expression of α7 nAChR and decreasing α3 and α4 nAChRs, which might play an important role in the pathogenesis of AD.
An
Yu
Y
Department of Molecular Biology, Guiyang Medical College, China.
Tang
Zhi
Z
Qi
Xiao-lan
XL
Xiao
Yan
Y
Shan
Ke-ren
KR
Guan
Zhi-zhong
ZZ
D000544:Alzheimer Disease / Q000235:genetics; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D000818:Animals; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism; D015536:Down-Regulation; D006801:Humans; D009447:Neuroblastoma / Q000378:metabolism* / Q000473:pathology; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D010957:Plasmids; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D064569:alpha7 Nicotinic Acetylcholine Receptor
D053829:Amyloid Precursor Protein Secretases; D016564:Amyloid beta-Protein Precursor; D012333:RNA, Messenger; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; C545487:APP protein, human; C579167:Chrna7 protein, human; C579165:Chrna7 protein, rat