Mitochondrial-targeted hydrogen sulfide donor, AP39 reduce hydrogen peroxide-induced mitochondrial dysfunction in human neuronal cells

Introduction: The accumulation of amyloid-β (Aβ) plaque in the brain is a characteristic feature of Alzheimer’s disease (AD) and the cause of fatal oxidative damage to neuronal cells. Korean red ginseng (RG) is used extensively in traditional medicine and is known to have anti-oxidative and anti-inflammatory properties. Objective: This study aims to investigate whether Korean RG extract inhibits Aβ-induced neuronal apoptosis. Methods: Human neuronal cells (SH-SY5Y cells) were stimulated with Aβ (5 μmol/L) and treated with RG dissolved in phosphate-buffered saline (0.2, 2, 20 μg/mL). Results: RG suppressed the reduction of cell viability and the increase in apoptotic factors (Bax/Bcl-2 ratio and caspase-3 activity) in Aβ-treated cells. RG suppressed Aβ-induced increases in intracellular and mitochondrial reactive oxygen species (ROS) levels and mitochondrial dysfunction (determined by low mitochondrial membrane potential and oxygen consumption rate) in a dose-dependent manner. RG inhibited nuclear factor kappa-light-chain-enhancer of activated B cells (NF-ĸB) activation and expression of the pro-apoptotic gene Nucling in Aβ-treated cells. Conclusion: RG confers protection against neuronal apoptosis by reducing ROS levels and suppressing mitochondrial dysfunction and NF-κB activation, which results in suppression of NF-κB-mediated activation of Nucling expression in Aβ-treated cells. Supplementation with RG may be beneficial for preventing Aβ-induced neuronal cell death associated with AD.

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Neurotoxicity and Neuroprotective Effects of Polyimides (PI) and Polyphenylenevinylene (PPV) against Hydrogen Peroxide (H2O2)

Scientific Research Journal ◽

10.24191/srj.v8i2.5049 ◽

2011 ◽

Vol 8 (2) ◽

pp. 33

Author(s):

Norfaezah Mazalan ◽

Mazatulikhma Mat Zain ◽

Nor Saliyana Jumali ◽

Norhanim Mohalid ◽

Zurina Shaameri ◽

...

Keyword(s):

Hydrogen Peroxide ◽

Drug Delivery Systems ◽

Neuronal Cells ◽

Water Soluble ◽

Brain Delivery ◽

Specific Therapy ◽

Neuroprotective Effects ◽

Water Soluble Polymer ◽

Site Specific ◽

Novel Drugs

Recently, research and development in the field of drug delivery systems (DDS) facilitating site-specific therapy has reached significant progression. DDS based on polymer micelles, coated micro- and nanoparticles, and various prodrug systems including water-soluble polymer have been prepared and extensively studied as novel drugs designed for cancer chemotherapy and brain delivery. Since polymers are going to be used in human, this study has the interest of testing two types of polymer, polyimides (PI) and polyphenylenevinylene (PPV) on neuronal cells. The objective of this study was to determine the possible neurotoxicity and potential neuroprotective effects of PI and PPV towards SH-SY5Y neuronal cells challenged by hydrogen peroxide (H2O2) as an oxidant. Cells were pretreated with either PI or PPV for 1 hour followed by incubation for 24 hour with 100 µM of H2O2. MTS assay was used to assess cell viability. Results show that PI and PPV are not harmful within the concentration up to 10 µM and 100 µM, respectively. However, PI and PPV do not protect neuronal cells against toxicity induced by H2O2 or further up the cell death.

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Hydrogen Peroxide Toxicity Induces Ras Signaling in Human Neuroblastoma SH-SY5Y Cultured Cells

Journal of Biomedicine and Biotechnology ◽

10.1155/2010/803815 ◽

2010 ◽

Vol 2010 ◽

pp. 1-4 ◽

Cited By ~ 7

Author(s):

Jirapa Chetsawang ◽

Piyarat Govitrapong ◽

Banthit Chetsawang

Keyword(s):

Hydrogen Peroxide ◽

Cell Viability ◽

Cultured Cells ◽

Neuronal Cells ◽

Competitive Inhibitor ◽

Ras Signaling ◽

Ras Proteins ◽

Human Neuroblastoma ◽

Dependent Signaling Pathway

It has been reported that overproduction of reactive oxygen species occurs after brain injury and mediates neuronal cells degeneration. In the present study, we examined the role of Ras signaling on hydrogen peroxide-induced neuronal cells degeneration in dopaminergic neuroblastoma SH-SY5Y cells. Hydrogen peroxide significantly reduced cell viability in SH-SY5Y cultured cells. An inhibitor of the enzyme that catalyzes the farnesylation of Ras proteins, FTI-277, and a competitive inhibitor of GTP-binding proteins, GDP-beta-S significantly decreased hydrogen peroxide-induced reduction in cell viability in SH-SY5Y cultured cells. The results of this study might indicate that a Ras-dependent signaling pathway plays a role in hydrogen peroxide-induced toxicity in neuronal cells.

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