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Prostaglandin A₂-induced Apoptosis is Not Inhibited by Heme Oygenase-1 in U2OS Cells
Kyoung-Won Ko(고경원),Sun-Young Lee(이선영),Ji-Hyun Ahn(안지현),Jaetaek Kim(김재택),In-Kyung Kim(김인경),Ho-Shik Kim(김호식) 한국생명과학회 2008 생명과학회지 Vol.18 No.11
Prostaglandin A₂ (PGA₂)는 사람 골육종 세포인 U2OS 세포주에서 apoptosis와 heme oxygenase (HO)-1의 발현을 함께 유도하였다. PGA₂에 의한 apoptosis는 HO-1의 과도한 발현이나 HO-1에 대한 small interfering RNA에 의한 발현저하에 의하여 변동되지 않았으나 H₂O₂에 의한 세포사망은 HO-1의 발현 수준에 반비례하여 변동되었다. 또한 thiol antioxidant인 N-acetyl-L-cysteine (NAC)은 PGA₂에 의한 세포사망과 HO-1의 발현 증가를 모두 차단하였지만, non-thiol antioxidant인 butylated hydroxyanisole (BHA)과 ascorbic acid는 세포사망과 HO-1의 발현 유도를 차단하지 않았다. 이와 같은 결과들은 PGA₂는 산화성 손상에 의해서가 아니라 PGA₂의 thiol-reactivity에 의하여 apoptosis와 HO-1의 발현을 유도하며, HO-1의 발현은 PGA₂에 의한 apoptosis와는 독립적인 현상이거나 기능적으로 apoptosis 유도의 하부에 위치하고 apoptosis의 진행에는 기여하지 않을 것이라는 것을 시사해 준다. Prostaglandin A₂ (PGA₂), one of cyclopentenone PGs, induced both apoptosis and heme oxygenase (HO)-1 expression in U2OS cells. PGA₂-induced apoptosis was not perturbed by either over-expression or knock-down of HO-1, whereas H₂O₂-induced cell death was inversely modulated by the expression level of HO-1. In addition, N-acetyl-L-cysteine (NAC), a thiol antioxidant, blocked both apoptosis and HO-1 expression induced by PGA₂. But, non-thiol antioxidants like butylated hydorxyanisole (BHA) and ascorbic acid did not block either apoptosis or HO-1-induction. Taken together, these results suggest that PGA₂ induces both apoptosis and HO-1 expression, which are critically related to the thiol-reactivity of PGA₂, but not oxidative stress, and HO-1 expression may be independent or functionally located downstream of apoptosis by PGA₂ without contribution to apoptosis progression.
Phenazine dioxide 유도체가 간 Xanthine Oxidase 활성에 미치는 영향
강일영(Il Young Kang),김상렬(Sang Yul Kim),김호식(Ho Shik Kim),허근(Keun Huh) 대한약학회 1990 약학회지 Vol.34 No.2
8-Acyl-2-hydroxyphenzaine-5,10-dioxides and 8-acyl-2-aminophenazine-5,10-dioxides bearing n-butanoyl, n-hexanoyl and n-octanoyl groups were synthesized. It was attempted to observe the effect of phenazine dioxide derivatives on the hepatic xanthine oxidase activity in this study. As the activity of xanthine oxidase, the key enzyme in the generation of superoxide anion radical (O2), was measured in the presence of phenazine dioxide derivatives, the action of 8-acyl-2-hydroxyphenazine-5,10-dioxide derivatives inhibited with increase of numbers of carbon atom bearing 8-acyl group. Moreover, when plotted on double reciprocal form, the Vmax value decrease as increase of numbers of carbon atom bearing acyl groups without affecting the Km value. However, the hepatic xanthine oxidase activity was not changed by 8-acyl-2-aminophenazine-5,10-dioxide derivatives.