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카드뮴투여 후 나타나는 치밀이음부와 상피세포의 변화

Changes of Tight Junction and Epithelial Cells after Treatment of Cadmium

김성수|김대진|정윤희|김경용|이원복|손동섭|이상진|조대윤
대한체질인류학회|2007.03|해부·생물인류학 (Anatomy & Biological Anthropology)|제20권 제1호|pp. 69-82|DOI 10.11637/aba.2007.20.1.69

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참고문헌

키워드

ZO-1OccludinTight junction카드뮴MDCK 세포치밀이음부ZO-2MDCK cellCdCl2
주제분류해부학

초록

카드뮴은 세포의 증식, 분화, 세포자멸 등에 영향을 주며 암을 유발시킨다. 카드뮴의 작용기전은 잘 알려 져 있지 않으며, 특히 치밀이음부에 대해서는 더욱 알려져 있지 않다. 그러므로 이 연구에서는 카드뮴의 상피세포 치밀이음부에 대한 연구에 대한 영향을 연구하고자 하였다. MDCK 세포배양에서 카드뮴을 투여하고 위상차현미경, TEER, 세포생존률, 공초점레이져현미경, 투과전자현미경 을 이용하여 배양세포와 치밀이음부의 변화를 관찰하였다. 카드뮴을 투여하면 TEER 가 감소되었으며, AlamarBlue Assay 결과, 역시 세포의 생존률이 감소되었다. 치밀이음 부는 세포사이연접에서 아래로 이동하면서 전자밀도가 낮아졌으며, 다른 세포와 인접한 부위에 있는 세포질의 두 께가 감소하였다. 최종적으로 세포의 사멸이 나타내기도 하였다. 공초점레이져현미경을 통해 관찰한 결과, occludin, ZO-1, ZO-2의 면역형광반응은 감소하고 불규칙해지는 경향을 나타내고 있었다. 이러한 변화는 시간과 농도에 비례하여 나타났다. 이러한 결과로 보면, 카드뮴을 투여하면 MDCK 세포장벽에서 투과성이 증가되고, 이것은 치밀이음부를 구성하 는 occludin, ZO-1, ZO-2 의 변화에서 오는 것으로 보인다.

Abstract

Cadmium (Cd) affects cell proliferation, differentiation, apoptosis and other cellular activities and can cause numerous molecular lesions that would be relevant to carcinogenesis. The mechanism of adverse effects of Cd has been poorly understood and, especially on the tight junction. Since there is rare information about the effect of Cd on tight junction protein, we here investigated whether Cd can alter the localization of the proteins. This study examined Cd effects on of tight junction (occludin, ZO-1, and ZO-2) using MDCK cell culture. The change of MDCK cell and tight junction was investigated after treatment of cadmium with phase contrast microscopy, TEER, cell viability, Transmission electron microscopy and confocal laser microscopy. After treatment of cadmium, transendothelial electrical resistance decreased with time and concentration dependent manner. AlamarBlue assay revealed that decreased cell viability also decreased with time and concentration dependent manner. The tight junction moved down between intercellular spaces with decreased density and the cellular thickness around cell junctions decreased with increasing concentration and exposure time of CdCl2. The MDCK cells eventually showed cell death with. Confocal laser microscopy revealed that immunofluorescent reaction of occludin, ZO-1 and ZO-2 decreased. Occludin, ZO-1 and ZO-2 were disrupted at tight junction. These data suggest that after treatment of Cd, increased permeability of MDCK cell monolayer increased. This might be accompanied with disruption of occludin, ZO-1 and ZO-2.

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