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. (5th October 2015)

• Record Type: Journal Article
• Authors: Lin, Chih-Li; Huang, Wen-Nung; Li, Hsin-Hua; Huang, Chien-Ning; Hsieh, Sam; Lai, Copper; Lu, Fung-Jou
• Is Part Of: Chemico-biological interactions. Volume 240(2015)
• Page Start: 12
• Page End: 21
• Publication Date: 2015-10-05
• Subjects: Amyloid β -- Hydrogen-rich water -- AMP-activated protein kinase -- Sirtuin 1 -- Forkhead box protein O3a; Biochemistry -- Periodicals; Toxicological chemistry -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biochimie -- Périodiques; Toxicologie biochimique -- Périodiques; 572
• DOI: 10.1016/j.cbi.2015.07.013
• Languages: English
• ISSNs: 0009-2797

Abstract

Abstract: 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. Highlights: HRW suppresses H2 O2 -generated ROS directly in vitro . HRW attenuates Aβ-induced neurotoxicity in cultured human neuronal cells. HRW upregulates Aβ-suppressed AMPK and downstream Sirt1-FoxO3a signaling. HRW reduces Aβ-induced ROS accumulation and upregulates intracellular antioxidative enzymes such as SOD1, SOD2, and catalase.