Protective effect of geranylgeranylacetone against hydrogen peroxide-induced oxidative stress in human neuroblastoma cells.

Abstract

AIMS:

Heat shock protein 70 (HSP70), one of the major HSPs, has been reported to suppress apoptosis and formation of pathogenic proteins in neurodegenerative disorders. Geranylgeranylacetone (GGA), an anti-ulcer drug, induces HSP70 and thereby protects against cellular damage in various diseases. We investigated the effect of GGA on hydrogen peroxide (H2O2)-induced neurotoxicity in human neuroblastoma SH-SY5Y cells.

MAIN METHODS:

H2O2-induced neuronal toxicity was measured by a CCK-8 assay and Hoechst 33342 staining. We also assessed oxidative stress and apoptosis by measuring reactive oxygen species (ROS) generation with 2′,7′-dichlorofluorescein diacetate (DCFH-DA), caspase-3 activity, and mitogen-activated protein kinase (MAPK) pathway.

KEY FINDINGS:

GGA showed a concentration-dependent inhibition on H2O2-induced apoptotic cell death. H2O2-induced induction of HSP70 was enhanced by GGA pretreatment. GGA effectively suppressed the up-regulation of Bax and down-regulation of Bcl-2. GGA also blocked the H2O2-induced phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2). In addition, GGA attenuated H2O2-induced ROS generation and caspase-3 activity.

SIGNIFICANCE:

These results demonstrate that GGA protects SH-SY5Y cells from H2O2-induced apoptosis, at least in part by enhancing HSP70 production. Neuroprotective properties of GGA indicate that this compound may be a potential therapeutic agent for the treatment and prevention of neurodegenerative diseases.

• Authors: Yun Ji Kim, Joo Youn Kim, Sang Wook Kang, Gae Sig Chun, Ju Yeon Ban
• Journal: Life sciences (Life Sci) Vol. 131 Pg. 51-6 (Jun 15 2015) ISSN: 1879-0631 [Electronic] Netherlands
• PMID: 25921766 (Publication Type: Journal Article)

Chemical References

• Anti-Ulcer Agents
• Diterpenes
• HSP70 Heat-Shock Proteins
• Reactive Oxygen Species
• Hydrogen Peroxide
• Mitogen-Activated Protein Kinases
• geranylgeranylacetone

Topics

• Anti-Ulcer Agents (pharmacology)
• Apoptosis (drug effects)
• Cell Line, Tumor
• Diterpenes (pharmacology)
• Down-Regulation (drug effects)
• HSP70 Heat-Shock Proteins (metabolism)
• Humans
• Hydrogen Peroxide (toxicity)
• Mitogen-Activated Protein Kinases (metabolism)
• Neuroblastoma (metabolism)
• Oxidative Stress (drug effects)
• Reactive Oxygen Species (metabolism)
• Up-Regulation (drug effects)