Alteration of proteins regulating apoptosis, Bcl-2, Bcl-x, Bax, Bak, Bad, ICH-1 and CPP32, in Alzheimer's disease.
Recently, apoptosis has been implicated in the selective neuronal loss of Alzheimer's disease (AD). Apoptosis is regulated by the B cell leukemia-2 gene product (Bcl-2) family (Bcl-2, Bcl-x, Bax, Bak and Bad) and the caspase family (ICH-1 and CPP32), with apoptosis being prevented by Bcl-2 and Bcl-x, and promoted by Bax, Bak, Bad, ICH-1 and CPP32. In the present study, we examined the levels of these proteins in the membranous and cytosolic fractions of temporal cortex in AD and control brain. In the membranous fraction, the levels of Bcl-2 alpha, Bcl-xL, Bcl-x beta, Bak and Bad were increased in AD. In the cytosolic fractions, the level of Bcl-x beta was increased, while Bcl-xL, Bax, Bak, and Bad and ICH-1L were unchanged. CPP32 was not detected in AD or control brain. These findings demonstrate a differential involvement of cell death-regulatory proteins in AD and suggest that Bak, Bad, Bcl-2 and Bcl-x are upregulated in AD brains.
Kitamura
Y
Y
Department of Neurobiology, Kyoto Pharmaceutical University, Japan.
Shimohama
S
S
Kamoshima
W
W
Ota
T
T
Matsuoka
Y
Y
Nomura
Y
Y
Smith
M A
MA
Perry
G
G
Whitehouse
P J
PJ
Taniguchi
T
T
D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism*; D017209:Apoptosis / Q000502:physiology*; D015153:Blotting, Western; D001923:Brain Chemistry; D002352:Carrier Proteins / Q000032:analysis / Q000378:metabolism; D053143:Caspase 2; D053148:Caspase 3; D020169:Caspases; D002458:Cell Fractionation; D002462:Cell Membrane / Q000737:chemistry; D003546:Cysteine Endopeptidases / Q000032:analysis / Q000378:metabolism; D003593:Cytoplasm / Q000737:chemistry; D004792:Enzyme Precursors / Q000032:analysis / Q000378:metabolism; D006624:Hippocampus / Q000737:chemistry / Q000201:enzymology; D006801:Humans; D008565:Membrane Proteins / Q000032:analysis / Q000378:metabolism; D008875:Middle Aged; D009410:Nerve Degeneration; D009447:Neuroblastoma; D011506:Proteins / Q000032:analysis / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis / Q000378:metabolism; D013702:Temporal Lobe / Q000737:chemistry / Q000201:enzymology; D013997:Time Factors; D014407:Tumor Cells, Cultured / Q000737:chemistry / Q000201:enzymology; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein; D051025:bcl-Associated Death Protein; D051020:bcl-X Protein
C494819:BAD protein, human; C494772:BAK1 protein, human; C494826:BAX protein, human; C494811:BCL2L1 protein, human; D002352:Carrier Proteins; D004792:Enzyme Precursors; D008565:Membrane Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein; D051025:bcl-Associated Death Protein; D051020:bcl-X Protein; C505407:CASP3 protein, human; D053143:Caspase 2; D053148:Caspase 3; D020169:Caspases; D003546:Cysteine Endopeptidases