간상피세포에서 BHT와 propyl gallate에 의한 gap junctional intercellular communication 억제 효과

Inhibition of Gap Junctional Intercellular Communication in Rat Liver Epithelial Cells Induced by BHT and Propyl Gallate

  • 발행 : 2007.10.31

초록

본 연구에서는 정상 세포인 간상피세포를 이용하여 BHT와 PG가 GJIC에 미치는 효과 및 그 작용 기전을 살펴보았다. BHT와 PG를 WB-F344세포에 각각 1.0mM, 0.75mM 이상 처리한 결과, 세포 생육이 80%이하로 저하되어 세포 독성을 보였고, BHT와 PG의 GJIC에 대한 억제효과는 이보다 낮은 농도인 0.6mM, 0.1mM에서 나타났으며 처리에 따른 Cx43 단백질의 발현 및 인산화를 측정한 결과, BHT와 PG 모두 농도의존적으로 Cx43의 인산화가 증가하였고, Cx43의 구조적 변화와 관련된 MAP kinase는 주요 biomarker인 ERK, p38, JNK의 발현 및 인산화를 측정한 결과, 농도의존적으로 ERK와 p38의 인산화가 증가하는 것으로 나타났다. 이는 WB-F344세포에 BHT와 PG의 처리가 세포독성을 나타내기 전 농도에서 GJIC의 억제하였음을 의미하며 이는 식품첨가물의 안전성 평가에도 활용될 수 있을 것으로 기대된다.

This study was conducted to analyze the cytotoxic effects of butylated hydroxytoluene (BHT) and propyl gallate (PG) in WB-F344 rat liver epithelial cells. Here we measured the inhibition level of gap junctional intercellular communication (GJIC) and elucidated the relationships between GJIC and mitogen-activated protein kinases (MAPKs) such as ERK, JNK, and p38. The cytotoxicities of BHT and PG appeared at concentrations of 1.0mM and 0.25mM, respectively, in the WB-F344 cells; and GJIC inhibition, which was analyzed by a scrape-loading/dye transfer assay and Western blotting analysis, appeared at 0.6mM for BHT and 0.1mM for PG, respectively. Also, the phosphorylations of Cx43, ERK, JNK, and p38 increased in dose-dependent manners. This suggests that BHT and PG treatments inhibited GJIC by the phosphorylation of MAPKs prior to cell damage.

키워드

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