组织转谷氨酰胺酶受细胞内钙离子长时间增加的调节，而非短暂钙离子增加的初始峰值的调节。

Regulation of tissue transglutaminase by prolonged increase of intracellular Ca2+, but not by initial peak of transient Ca2+ increase.

作者信息

Yoo Je-Ok, Yi Sun-Ju, Choi Hyun Jung, Kim Woo Jin, Kim Young-Myeong, Han Jeong-A, Ha Kwon-Soo

机构信息

Department of Molecular and Cellular Biochemistry, Kangwon National University College of Medicine, Chunchon, Republic of Korea.

出版信息

Biochem Biophys Res Commun. 2005 Nov 18;337(2):655-62. doi: 10.1016/j.bbrc.2005.09.108. Epub 2005 Sep 26.

DOI:10.1016/j.bbrc.2005.09.108

PMID:16212941

Abstract

Tissue transglutaminase (tTGase) is a member of calcium-dependent transamidation enzyme family, but a detailed regulation mechanism of tTGase by intracellular Ca(2+) is not clearly understood. Arachidonic acid (AA) and maitotoxin (MTX) activated tTGase in a dose- and time-dependent manner. Transfection of tTGase siRNA largely inhibited tTGase expression and tTGase activation by MTX. AA induced an initial increase of intracellular Ca(2+) followed by a prolonged increase. Removal of extracellular Ca(2+) with EGTA blocked the prolonged Ca(2+) increase in response to AA, although the initial Ca(2+) increase remained. In contrast, EGTA completely blocked the increase of intracellular Ca(2+) by MTX. The activation of tTGase by AA or MTX was significantly inhibited by EGTA. Moreover, EGTA prevented the prolonged increase of intracellular Ca(2+) and tTGase activation by lysophosphatidic acid, but had no effect on the initial Ca(2+) increase. These results suggested that tTGase is regulated by the prolonged increase of intracellular Ca(2+) originated from Ca(2+) influx, rather than by the initial peak of transient Ca(2+) increase.

摘要

组织转谷氨酰胺酶（tTGase）是钙依赖性转酰胺酶家族的一员，但细胞内Ca(2+)对tTGase的详细调节机制尚不清楚。花生四烯酸（AA）和刺尾鱼毒素（MTX）以剂量和时间依赖性方式激活tTGase。转染tTGase小干扰RNA（siRNA）可在很大程度上抑制tTGase表达以及MTX对tTGase的激活。AA诱导细胞内Ca(2+)先出现初始升高，随后持续升高。用乙二醇双四乙酸（EGTA）去除细胞外Ca(2+)可阻断AA诱导的Ca(2+)持续升高，尽管初始Ca(2+)升高仍然存在。相反，EGTA完全阻断了MTX引起的细胞内Ca(2+)升高。EGTA显著抑制了AA或MTX对tTGase的激活。此外，EGTA可防止溶血磷脂酸引起的细胞内Ca(2+)持续升高和tTGase激活，但对初始Ca(2+)升高没有影响。这些结果表明，tTGase受源自Ca(2+)内流的细胞内Ca(2+)持续升高调节，而非受瞬时Ca(2+)升高的初始峰值调节。