MRE结合转录因子-1在内毒素血症期间被激活：金属硫蛋白的核心作用。

MRE-binding transcription factor-1 is activated during endotoxemia: a central role for metallothionein.

作者信息

Kimura Tomoki, Itoh Norio, Takehara Miyako, Oguro Ikuyo, Ishizaki Jun-ichi, Nakanishi Tsuyoshi, Tanaka Keiichi

机构信息

Department of Toxicology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6, Yamada-oka, Suita, Osaka 565-0871, Japan.

出版信息

Toxicol Lett. 2002 Mar 24;129(1-2):77-84. doi: 10.1016/s0378-4274(01)00473-8.

DOI:10.1016/s0378-4274(01)00473-8

PMID:11879976

Abstract

Endotoxin (LPS) has been established to induce hepatic metallothionein (MT), but the specific role of MT remains unknown. In this study, we examined whether MT can modulate MTF-1 activity during endotoxemia. Treatment with IL-6, the main mediator of MT induction during endotoxemia, enhanced the expression of the MRE(d)-driven reporter gene. MTF-1 DNA-binding activity was increased 16-24 h after LPS administration in wild-type mice, while no such activation was observed in MT-null mice during the same period. The expression of alpha(1)-acid glycoprotein (AGP) mRNA, an RNA regulated by MTF-1, was lower in MT-null than in wild-type mice. Our results suggested that MTF-1 was activated during endotoxemia. MT can act as an activator of MTF-1, and MT can induce MTF-1 targeted gene expression during endotoxemia.

摘要

内毒素（脂多糖，LPS）已被证实可诱导肝脏金属硫蛋白（MT），但其具体作用尚不清楚。在本研究中，我们检测了MT是否能在内毒素血症期间调节金属反应元件结合转录因子1（MTF-1）的活性。在内毒素血症期间，白细胞介素-6（IL-6）是诱导MT的主要介质，用其处理可增强金属反应元件（MRE）驱动的报告基因的表达。在野生型小鼠中，LPS给药后16 - 24小时MTF-1的DNA结合活性增加，而在同一时期，MT基因敲除小鼠中未观察到这种激活。MTF-1调节的α(1)-酸性糖蛋白（AGP）mRNA的表达在MT基因敲除小鼠中低于野生型小鼠。我们的结果表明，MTF-在内毒素血症期间被激活。MT可作为MTF-1的激活剂，并且MT可在内毒素血症期间诱导MTF-1靶向基因的表达。