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심바스타틴이 인체망막색소상피세포에서 카탈라아제 발현에 미치는 영향

The Effect of Simvastatin on the Expression of Catalase in Human Retinal Pigment Epithelial Cells

이소영|진희승|강민구
대한안과학회 (The Korean Ophthalmological Society)|2014.10|대한안과학회지 (Journal of The Korean Ophthalmological Society)|제55권 제10호|pp. 1535-1542

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Oxidative stressCatalaseSimvastatinRetinal pigment epithelium
주제분류안과학

초록

목적: 심바스타틴이 인체망막색소상피세포에서 항산화 효소인 카탈라아제(catalase)의 발현에 어떤 영향을 미치는지 알아보고자 한다. 대상과 방법: 배양한 인체망막색소상피세포에 심바스타틴을 농도별로 각각 6시간, 24시간 동안 노출시킨 후 real-time PCR과catalase assay를 통해 catalase의 mRNA의 발현 정도와 활성도를 관찰하였다. 인체망막색소상피세포에 과산화수소 200 μM와 심바스타틴을 농도별로 노출시킨 후 real-time PCR과 catalase assay를 통해 catalase의 mRNA의 발현 정도와 활성도를 관찰하였다. 또한 형광이용세포분류기를 이용하여 세포 내 활성산소를 측정하였다. 결과: 인체망막색소상피세포에 심바스타틴을 노출시켰을 때 10 μM까지 농도에 비례하여 catalase의 mRNA와 활성도가 증가하는 것을 확인할 수 있었다. 과산화수소 200 μM를 전처치한 인체망막색소상피세포에서는 2.5 μM의 심바스타틴에 노출되었을 때 catalase의 mRNA가 가장 높게 증가하였고, 5 μM의 심바스타틴에 노출되었을 때 catalase의 활성도가 가장 높게 증가하였다. 심바스타틴에의한 활성산소 감소 효과는 catalase의 억제제인 3-Amino-1,2,4-triazole (3-AT)을 함께 처치하였을 때 복귀되었다. 결론: 인체망막색소상피세포에서 심바스타틴은 catalase의 발현을 증가시킴으로써 항산화 효과를 나타낸다. 이러한 심바스타틴의 항산화 효과는 산화스트레스에 의해 유발되는 연령관련 황반변성의 예방에 이용될 수 있을 것으로 기대된다.

Abstract

Purpose: To evaluate the effects of simvastatin on the catalase expression in human retinal pigment epithelium. Methods: Retinal pigment epithelial (RPE) cells were incubated for 6 hours and 24 hours with various concentrations ofsimvastatin. In addition, RPE cells were incubated with 200 μM of H2O2 and various concentrations of simvastatin. After incubation,real-time polymerase chain reaction (PCR) was performed to examine the catalase messenger ribonucleic acid(mRNA) expression and a catalase assay was performed to examine the catalase activity in RPE. Intracellular reactive oxygenspecies (ROS) was measured using a fluorescence activated cell sorter (FACS). Results: Simvastatin increased the amount of catalase mRNA and catalase activity at 10 μM in RPE cells. Under oxidative stress(200 μM of H2O2), 2.5 μM of simvastatin increased the catalase mRNA expression and 5 μM of simvastatin increased catalaseactivity in RPE cells. In addition, simvastatin reduced free radical formation but this effect was diminished in the presence of anirreversible catalase inhibitor, 3-amino-1,2,4-triazole (3-AT). Conclusions: Simvastatin exhibits anti-oxidative effects by inducing the catalase expression in human RPE cells. This anti-oxidativeeffect may be beneficial for preventing age-related macular degeneration induced by oxidative stress.

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