Association of ABCA2 expression with determinants of Alzheimer's disease.
With the use of a novel method for detecting differential gene expression, alterations in functional gene clusters related to transport or oxidative stress response and beta-amyloid (Abeta) peptide metabolism were identified in a HEK293 cell line engineered to overexpress the human ATP binding cassette transporter ABCA2. These included fatty acid binding protein, phospholipid binding protein, phospholipid synthesis protein, transporter cofactors, seladin-1, Abeta precursor protein (APP), vimentin, and low-density lipoprotein receptor-related protein. ABCA2 was highly expressed in neuroblastoma cells and colocalized with Abeta and APP. Additionally, increased APP protein levels were detected within ABCA2/APP double-transfected cells, and increased Abeta was detected in the media of ABCA2-transfected cells relative to controls. The transporter was abundant in the temporal and frontal regions of both normal and Alzheimer's disease (AD) brain but was detected at lower concentrations in the parietal, occipital, and cerebellar regions. The ABCA2 transfected cell line expressed resistance to a free radical initiator, confirming involvement in protection against reactive oxygen species and suggesting a further possible link to AD.
Chen
Zhijian J
ZJ
Department of Pharmacology, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA.
Vulevic
Bojana
B
Ile
Kristina E
KE
Soulika
Athena
A
Davis
Warren
W
Reiner
Peter B
PB
Connop
Bruce P
BP
Nathwani
Parimal
P
Trojanowski
John Q
JQ
Tew
Kenneth D
KD
D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis / Q000235:genetics*; D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism; D000578:Amidines / Q000494:pharmacology; D016564:Amyloid beta-Protein Precursor / Q000096:biosynthesis / Q000235:genetics; D001692:Biological Transport / Q000235:genetics; D002460:Cell Line / Q000187:drug effects / Q000378:metabolism; D045744:Cell Line, Tumor / Q000187:drug effects / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007668:Kidney; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics; D009447:Neuroblastoma / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D018384:Oxidative Stress / Q000235:genetics; D017382:Reactive Oxygen Species; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics; D014162:Transfection
C418186:ABCA2 protein, human; D018528:ATP-Binding Cassette Transporters; D000578:Amidines; D016564:Amyloid beta-Protein Precursor; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D017382:Reactive Oxygen Species; D011993:Recombinant Fusion Proteins; C046728:2,2'-azobis(2-amidinopropane)