Hydrogen-rich water attenuates amyloid β-induced cytotoxicity through upregulation of Sirt1-FoxO3a by stimulation of AMP-activated protein kinase in SK-N-MC cells.
Amyloid β (Aβ) peptides are identified in cause of neurodegenerative diseases such as Alzheimer's disease (AD). Previous evidence suggests Aβ-induced neurotoxicity is linked to the stimulation of reactive oxygen species (ROS) production. The accumulation of Aβ-induced ROS leads to increased mitochondrial dysfunction and triggers apoptotic cell death. This suggests antioxidant therapies may be beneficial for preventing ROS-related diseases such as AD. Recently, hydrogen-rich water (HRW) has been proven effective in treating oxidative stress-induced disorders because of its ROS-scavenging abilities. However, the precise molecular mechanisms whereby HRW prevents neuronal death are still unclear. In the present study, we evaluated the putative pathways by which HRW protects against Aβ-induced cytotoxicity. Our results indicated that HRW directly counteracts oxidative damage by neutralizing excessive ROS, leading to the alleviation of Aβ-induced cell death. In addition, HRW also stimulated AMP-activated protein kinase (AMPK) in a sirtuin 1 (Sirt1)-dependent pathway, which upregulates forkhead box protein O3a (FoxO3a) downstream antioxidant response and diminishes Aβ-induced mitochondrial potential loss and oxidative stress. Taken together, our findings suggest that HRW may have potential therapeutic value to inhibit Aβ-induced neurotoxicity.
Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan; Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan.
Chih-Li
CL
Lin
Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
Wen-Nung
WN
Huang
Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
Hsin-Hua
HH
Li
Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
Chien-Ning
CN
Huang
Unitira Applied Materials Corp., Taipei, Taiwan.
Sam
S
Hsieh
Fluxtek International Corp., Pingtung, Taiwan.
Copper
C
Lai
Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan; School of Medical Applied Chemistry, Chung Shan Medical University, Taichung, Taiwan. Electronic address: fjlu@csmu.edu.tw.
Fung-Jou
FJ
Lu
D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000235:genetics* / Q000378:metabolism; D016166:Free Radical Scavengers / Q000494:pharmacology; D006801:Humans; D006859:Hydrogen / Q000494:pharmacology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism*; D056564:Sirtuin 1 / Q000235:genetics* / Q000378:metabolism; D014867:Water / Q000737:chemistry / Q000494:pharmacology
D016229:Amyloid beta-Peptides; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; C474033:FoxO3 protein, mouse; D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D014867:Water; D006859:Hydrogen; D055372:AMP-Activated Protein Kinases; D056564:Sirtuin 1
AMP-activated protein kinase; Amyloid β; Forkhead box protein O3a; Hydrogen-rich water; Sirtuin 1