Protective effects of peroxiredoxin 6 overexpression on amyloid β-induced apoptosis in PC12 cells.
Oxidative stress triggered by amyloid beta (Aβ) accumulation contributes substantially to the pathogenesis of Alzheimer's disease (AD). In the present study, we examined the involvement of the antioxidant activity of peroxiredoxin 6 (Prdx 6) in protecting against Aβ25-35-induced neurotoxicity in rat PC12 cells. Treatment of PC12 cells with Aβ25-35 resulted in a dose- and time-dependent cytotoxicity that was associated with increased accumulation of intracellular reactive oxygen species (ROS) and mitochondria-mediated apoptotic cell death, including activation of Caspase 3 and 9, inactivation of poly ADP-ribosyl polymerse (PARP), and dysregulation of Bcl-2 and Bax. This apoptotic signaling machinery was markedly attenuated in PC12 cells that overexpress wild-type Prdx 6, but not in cells that overexpress the C47S catalytic mutant of Prdx 6. This indicates that the peroxidase activity of Prdx 6 protects PC12 cells from Aβ25-35-induced neurotoxicity. The neuroprotective role of the antioxidant Prdx 6 suggests its therapeutic and/or prophylactic potential to slow the progression of AD and limit the extent of neuronal cell death caused by AD.
Asan Institute for Life Sciences, University of Ulsan College of Medicine, Asan Medical Center , Seoul , Republic of Korea.
I K
IK
Kim
K J
KJ
Lee
S
S
Rhee
S B
SB
Seo
J H
JH
Pak
D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000682:Amyloid / Q000378:metabolism* / Q000494:pharmacology; D016229:Amyloid beta-Peptides / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D020030:Nitric Oxide Donors / Q000494:pharmacology; D018384:Oxidative Stress / Q000502:physiology; D016716:PC12 Cells; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology*; D054465:Peroxiredoxin VI / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D014162:Transfection
D000682:Amyloid; D016229:Amyloid beta-Peptides; D020030:Nitric Oxide Donors; D010446:Peptide Fragments; D017382:Reactive Oxygen Species; C074636:amyloid beta-protein (25-35); D054465:Peroxiredoxin VI