A novel splice variant of occludin deleted in exon 9 and its role in cell apoptosis and invasion

被引:23
作者
Gu, Jin-Mo [1 ,2 ]
Lim, Seung Oe [1 ,2 ]
Park, Young Min [3 ,4 ]
Jung, Guhung [1 ,2 ]
机构
[1] Seoul Natl Univ, Seoul 151747, South Korea
[2] Dept Biol Sci, Seoul 151747, South Korea
[3] Bundang Jesaeng Gen Hosp, Hepatol Ctr, Kyonggi Do, South Korea
[4] Bundang Jesaeng Gen Hosp, Lab Hepatocarcinogenesis, Kyonggi Do, South Korea
关键词
apoptosis; calcium; invasion; occludin; splice variant;
D O I
10.1111/j.1742-4658.2008.06467.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The tight junction protein occludin participates in cell adhesion and migration and has been shown to possess antitumorigenic properties; however, the exact mechanism underlying these effects is poorly understood. In liver cell lines, we identified an occludin splice variant deleted in exon 9 (Occ(Delta E9)). Furthermore, comparison analysis of wild-type occludin (Occ(WT)) and Occ(Delta E9) revealed that exon 9 played important roles in the induction of mitochondria-mediated apoptosis and the inhibition of invasion, along with the downregulation of matrix metalloproteinase expression. In addition, by using the calcium indicator X-rhod-1, and the inositol trisphosphate receptor inhibitor 2-aminoethoxydiphenyl borate, we found that Occ(WT) but not Occ(Delta E9) increased calcium release from the endoplasmic reticulum. In conclusion, our results showed that occludin mediates apoptosis and invasion by elevating the cytoplasmic calcium concentration and that exon 9 of occludin is an important region that mediates these effects.
引用
收藏
页码:3145 / 3156
页数:12
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