산화스트레스에 의한 치밀이음부 zonular occludens-1 발현의 변화
Oxidative stress induced-expression changes of zonular occludens-1 in thight junction
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중추신경계속에서 미세환경의 항상성은 뇌의 정상적인 활동에 필수적이며, 혈액뇌장벽에 의해 유지된다. 치밀이음부의 zonular occludens-1 (ZO-1)은 혈액뇌장벽에서 내피세피 이온과의 용질장벽으로 중요한 역할을 하 는 것으로 알려져 있다. 활성산소종으로 인한 혈액뇌장벽의 기능이상은 치밀이음부의 기능부전에 기인한다. 이 연 구에서는 소의 뇌 미세혈관내피세포의 일차배양을 통해 H2O2에 의해 일어나는 세포간 물질투과도의 변화와 치밀 이음부 복합체를 형성하는 ZO-1의 변화를 알아보고자 하였다. 전기저항으로 측정한 혈액뇌장벽 투과도는 H2O2 의 농도(0.01, 0.1, 1.0 mM)와 노출시간에 비례하여 증가하였다. 또한 H2O2 1 mM 이하 및 4시간 내에서 세포생존 율에 변화는 없었다. H2O2에 의해 치밀이음부에서 ZO-1이 불규칙하게 소실되었으나 ZO-1의 단백질 양에는 변 화가 없었다. 요약하면 H2O2는 혈액뇌장벽에서 세포간 투과도를 증가시키며, 이는 ZO-1의 단백질의 분포의 변화 에 밀접한 관계가 있다고 할 수 있다.
Abstract
The homeostasis of microenvironment in central nervous system, essential for normal function, is maintained by blood-brain barrier (BBB). ZO-1 in tight junctions (TJs) plays an important role in maintaining BBB endothelial ion and solute barriers. Malfunction of BBB by reactive oxygen species has been attributed to disruption of TJs. This study examined H2O2 effects on paracellular permeability and changes in TJ protein ZO-1 using primary culture of bovine brain microvessel endothelial cells. The BBB permeability,measured as TER, increased in a dose-and time-dependent manner when treated with H2O2 (0.01, 0.1, 1.0 mM). Cytotoxicity test revealed that H2O2 did not cause cell death below 1 mM H2O2 within 4 hr. H2O2 caused intermittent disruption and loss of ZO-1 at tight junctions, but ZO-1 maintained steady state levels of expression. In conclusion, we report that H2O2 induces increased paracellular permeability of BBB that is accompanied with alterations in localization of ZO-1.
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