위선세포의 항산화 방어기전으로의 Nitric Oxide의 역할

Role of Nitric Oxide as an Antioxidant in the Defense of Gastric Cells

위점막은 위강내에서 생성되는 독성이 강한 활성산소종에 노출된다. Nitric oxide는 glutathione의 항상성을 유지시킴으로써 acetaminophen 유도 간독성에 대한 보호효과를 나타내었다. 본 연구는 hydrogen peroxide로 인한 위선세포 손상에 대한 nitric oxide의 작용을 규명하고자 하였다. Hydrogen peroxide는 ${\beta}-D-glucose$와 glucose oxidase의 반응에 의해 생성시켰으며, 위선세포에 L-arginine, $N^{G}-nitro-L-arginine$ methyl ester 및 $N^G-nitro-L-arginine$을 전처리 한 후, 세포외로 유리되는 지질과산화물 및 nitrite를 정량하고 세포내 glutathione 함량을 측정하였다. 결과로서, glucose/glucose oxidase를 처리한 경우 glucose oxidase 농도의존적으로 지질과산화물 생성은 증가되었으며, nitrite 유리 및 glutathione 함량은 감소되었다. NO synthase의 기질인 L-arginine 전처리시 glucose/glucose oxidase에 의한 지질과산화 및 nitrite 유리 증가와 세포내 glutathione 감소등이 방지되었다. $N^G-nitro-L-arginine$ methyl ester 및 $N^G-nitro-L-arginine$등 NO synthase 억제제들은 세포손상에 보호효과를 나타내지 않았다. 결론적으로 nitric oxide는 hydrogen peroxide로 인한 세포손상에 대한 보호효과가 없으며, 이는 지질과산화 반응 및 세포내 glutathione 고갈등을 억제시킴으로써 이루어진다고 사료된다.

Gatric mucosa is exposed to toxic, reactive oxygen species generated within the lumen. Nitric oxide protected acetaminophen-induced hepatotoxicity by maintaining glutathione homeostasis. The present study examined the role of nitric oxide in mediating hydrogen peroxide - induced damage to gastric cells. Hydrogen peroxide was generated by glucose oxidase acting on ${\beta}-D-glucose$. L-arginine, $N^G-nitro-L-arginine$ methyl ester, or $N^G-nitro-L-arginine$ were treated to the cells with glucose/glucose oxidase. Lipid peroxidation and nitrite release and cellular content of glutathione were determined. As a result, dose - dependent increase in lipid peroxide production as well as dose - dependent decrease in nitrite release and cellular glutathione content were observed in glucose/glucose oxidase - treated cells. Pretreatment of L-arginine, a substrate for nitric oxide synthase, prevented the increase of lipid peroxide production and the reduction of nitrite release as well as glutathione content. Inhibitors of nitric oxide synthase such as $N^G-nitro-L-arginine$ methyl ester and $N^G-nitro-L-arginine$ did not protect hydrogen peroxide - induced cell damage. In conclusion, nitric oxide protects gestric cells from hydrogen peroxide possibly by inhibiting lipid peroxidation and by preserving cellular glutathione stores.