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


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.


RESULTS
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.


CONCLUSIONS
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.
Department of Dental Pharmacology, School of Dentistry, Dankook University, Cheonan, Republic of Korea.
Yun Ji
YJ
Kim
Division for Healthcare Technology Assessment Research, National Evidence-based Healthcare Collaborating Agency (NECA), Seoul, Republic of Korea.
Joo Youn
JY
Kim
Kohwang Medical Research Institute, School of Medicine, Kyung Hee University, Seoul, Republic of Korea.
Sang Wook
SW
Kang
Department of Oral Physiology, School of Dentistry, Dankook University, Cheonan, Republic of Korea.
Gae Sig
GS
Chun
Department of Dental Pharmacology, School of Dentistry, Dankook University, Cheonan, Republic of Korea. Electronic address: jyban@dankook.ac.kr.
Ju Yeon
JY
Ban
D000897:Anti-Ulcer Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D004224:Diterpenes / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009447:Neuroblastoma / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
D000897:Anti-Ulcer Agents; D004224:Diterpenes; D018840:HSP70 Heat-Shock Proteins; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D020928:Mitogen-Activated Protein Kinases; C031049:geranylgeranylacetone
Geranylgeranylacetone; Heat shock protein 70; Hydrogen peroxide; Neuroblastoma