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Neuroprotective and neurite outgrowth effects of maltol on retinal ganglion cells under oxidative stress

 Samin Hong  ;  Yoko Iizuka  ;  Taekjune Lee  ;  Chan Yun Kim  ;  Gong Je Seong 
 MOLECULAR VISION, Vol.20(1) : 1456-1462, 2014 
Journal Title
Issue Date
Animals ; Animals, Newborn ; Apoptosis/drug effects ; Cell Survival/drug effects ; Dose-Response Relationship, Drug ; Gene Expression ; Hydrogen Peroxide/antagonists & inhibitors ; Hydrogen Peroxide/pharmacology ; In Situ Nick-End Labeling ; Mice ; NF-kappa B/genetics ; NF-kappa B/metabolism ; Neurites/drug effects* ; Neurites/metabolism ; Neuroprotective Agents/pharmacology* ; Oxidative Stress ; Primary Cell Culture ; Pyrones/pharmacology* ; Retinal Ganglion Cells/cytology ; Retinal Ganglion Cells/drug effects* ; Retinal Ganglion Cells/metabolism ; Signal Transduction ; Tubulin/genetics ; Tubulin/metabolism
PURPOSE: To evaluate the neuroprotective and neurite outgrowth effects of maltol, a natural aroma compound, on retinal ganglion cells (RGCs) under oxidative stress in vitro. METHODS: Mouse primary RGCs were isolated using immunopanning-magnetic separation and exposed to H2O2 in the presence of maltol. The cell viability and apoptosis were determined by using adenosine 5'-triphosphate (ATP) assay and terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL), respectively. Neurite outgrowth was assessed by immunofluorescence for α-tubulin. The activation of nuclear factor-κB (NF-κB) was also evaluated using immunofluorescence. RESULTS: When the RGCs were exposed to 20 μM of H2O2 for 16 h, their viability dropped to 40.3±3.4%. However, the maltol treatment restored the cells in a dose-dependent manner. The viability recovered to 73.9±5.1% with 10 μM of maltol and even reached 175.1±11.3% with 2 mM of maltol, as measured by ATP assay. This oxidative stress significantly increased the number of TUNEL-positive RGCs, but the maltol drastically reduced the proportion of those apoptotic cells. The oxidative stress hampered the neurite outgrowth of the RGCs, whereas maltol restored their ability to sprout neurites. Regarding NF-κB, the active form of phosphorylated NF-κB (pNF-κB) increased the oxidative stress level but the maltol treatment again reduced it to an unstressful level. CONCLUSIONS: Our data revealed that maltol attenuated the oxidative stress-induced injury in the primary mouse RGCs. Its neuroprotective and neurite outgrowth effects seemed to be related to NF-κB signaling. Maltol has potential as a new neuroprotective therapeutic agent for oxidative stress-related ocular diseases, including glaucoma.
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1. College of Medicine (의과대학) > Dept. of Ophthalmology (안과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
Kim, Chan Yun(김찬윤) ORCID logo https://orcid.org/0000-0002-8373-9999
Seong, Gong Je(성공제) ORCID logo https://orcid.org/0000-0002-5456-4296
Iizuka, Yoko(이주카요코)
Hong, Sa Min(홍사민)
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