Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Glucose Oxidase/glucose Induces Apoptosis in C6 Glial Cells via Mitochondria-dependent Pathway

  • PARK Min Kyu (Department of Pharmacology, College of medicine, Gyeongsang National University) ;
  • KIM Woo Sang (Department of Pharmacology, College of medicine, Gyeongsang National University) ;
  • LEE Young Soo (Department of Pharmacology, College of medicine, Gyeongsang National University) ;
  • KANG Young Jin (Department of Pharmacology, College of Medicine, Yeungnam University) ;
  • CHONG Won Seog (Department of Pharmacology, College of Medicine, Seonam University) ;
  • KIM Hye Jung (Department of Pharmacology, College of medicine, Gyeongsang National University) ;
  • SEO Han Geuk (Department of Pharmacology, College of medicine, Gyeongsang National University) ;
  • LEE Jae Heun (Department of Pharmacology, College of medicine, Gyeongsang National University) ;
  • CHANG Ki Churl (Department of Pharmacology, College of medicine, Gyeongsang National University)
  • Published : 2005.12.01
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Abstract

It has been proposed that reactive oxygen species (ROS), mainly superoxide anion ($O_2^-$) and hydrogen peroxide ($H_2O_2$), may mediate oxidative stress. Production of $H_2O_2$ during oxidative phosphorylation, inflammation, and ischemia can cause oxidative stress leading to cell death. Although glucose oxidase (GOX) in the presence of glucose continuously generates $H_2O_2$, it is not clear whether GOX produces apoptotic cell death in C6 glial cells. Thus, we investigated the mechanism by which GOX induces cell death. Cells were incubated with different concentration of GOX in the presence of glucose where cell viability, TUNEL and DNA ladder were analyzed. Results indicated that GOX exhibited cytotoxicity in a dose dependent manner by MTT assay. TUNEL positive cell and DNA laddering showed that GOX-induced cytotoxicity was due to apoptosis. Western blot analysis also showed that the cleaved caspase-3 level was detected in the GOX-treated cells at 10 mU/ml and increased dramatically at 30 mU/ml. Cleaved PARP also appeared at 10 mU/ml and lasted at 20 or 30 mU/ml of GOX. Cytochrome c level was increased by GOX dose dependently, which was contrast to Bcl-2 expression level. These results suggest that GOX induces apoptosis through caspase-3 activation, which followed by cytochrome c release from mitochondria through regulating of Bcl-2 level.

Keywords

References

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