Beta-Amyloid Oligomers Activate Apoptotic BAK Pore for Cytochrome c Release

Title
Beta-Amyloid Oligomers Activate Apoptotic BAK Pore for Cytochrome c Release
Authors
김재욱양유수송승수나정현오경준정철현유연규신년균
Keywords
apoptosis; BAK; beta-amyloid; cytochrome c release
Issue Date
2014-10
Publisher
Biophysical journal
Citation
VOL 107, NO 7, 1601-1608
Abstract
In Alzheimer’s disease, cytochrome c-dependent apoptosis is a crucial pathway in neuronal cell death. Although beta-amyloid (Aβ) oligomers are known to be the neurotoxins responsible for neuronal cell death, the underlying mechanisms remain largely elusive. Here, we report that the oligomeric form of synthetic Aβ of 42 amino acids elicits death of HT-22 cells. But, when expression of a bcl-2 family protein BAK is suppressed by siRNA, Aβ oligomer-induced cell death was reduced. Furthermore, significant reduction of cytochrome c release was observed with mitochondria isolated from BAK siRNA-treated HT-22 cells. Our in vitro experiments demonstrate that Aβ oligomers bind to BAK on the membrane and induce apoptotic BAK pores and cytochrome c release. Thus, the results suggest that Aβ oligomers function as apoptotic ligands and hijack the intrinsic apoptotic pathway to cause unintended neuronal cell death.
URI
http://pubs.kist.re.kr/handle/201004/48677
ISSN
00063495
Appears in Collections:
KIST Publication > Article
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