Zinc diethyldithiocarbamate as an inducer of metallothionein in cultured vascular endothelial cells

被引：13

作者：

Fujie, Tomoya ^{[1
]}

Segawa, Yukino ^{[1
]}

Uehara, Akane ^{[1
]}

Nakamura, Takehiro ^{[1
]}

Kimura, Tomoki ^{[2
]}

Yoshida, Eiko ^{[1
]}

Yamamoto, Chika ^{[3
]}

Uchiyama, Masanobu ^{[4
]}

Naka, Hiroshi ^{[5
,6
]}

Kaji, Toshiyuki ^{[1
]}

机构：

[1] Tokyo Univ Sci, Fac Pharmaceut Sci, Dept Environm Hlth, 2641 Yamazaki, Noda, Chiba 2788510, Japan

[2] Setsunan Univ, Dept Life Sci, Fac Sci & Engn, 17-8 Ikedanakamachi, Neyagawa, Osaka 5730101, Japan

[3] Toho Univ, Fac Pharmaceut Sci, Dept Environm Hlth, 2-2-1 Miyama, Funabashi, Chiba 2748510, Japan

[4] Univ Tokyo, Grad Sch Pharmaceut Sci, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1130033, Japan

[5] Nagoya Univ, Grad Sch Sci, Chikusa Ku, Nagoya, Aichi 4648602, Japan

[6] Nagoya Univ, Res Ctr Mat Sci, Chikusa Ku, Nagoya, Aichi 4648602, Japan

来源：

JOURNAL OF TOXICOLOGICAL SCIENCES | 2016年 / 41卷 / 02期

关键词：

Antioxidant response element; Metallothionein; Metal response element; Vascular endothelial cell; Zinc; Zinc complex; ANTIOXIDANT RESPONSE ELEMENT; TRANSCRIPTION FACTOR-I; CADMIUM CYTOTOXICITY; DNA-BINDING; INDUCTION; GENE; ACTIVATION; PROTECTION; NRF2; MOLECULES;

D O I：

10.2131/jts.41.217

中图分类号：

R99 [毒物学（毒理学）];

学科分类号：

100405 ;

摘要：

Vascular endothelial cells are in direct contact with blood. Inorganic zinc is thought to be incapable of inducing metallothionein, which protects cells from heavy metal toxicity and oxidative stress, in vascular endothelial cells. Here, we aimed to further characterize the induction of metallothionein in vascular endothelial cells. Our results confirmed that inorganic zinc could not induce metallothionein in vascular endothelial cells. Moreover, ZnSO4 could not activate both the metal response element (MRE) transcription factor 1 (MTF-1)/MRE and Nrf2/antioxidant response element (ARE) pathways and was incapable of inducing metallothionein. In addition, bis(L-cysteinato)zincate(II), a zinc complex that activates the MTF-1/MRE pathway, increased MRE promoter activity but failed to induce metallothionein, suggesting that vascular endothelial metallothionein was not induced only by activation of the MTF-1/MRE pathway. Further analysis of a library of zinc complexes showed that zinc(II) bis(diethyldithiocarbamate) activated the MTF-1/MRE pathway but not the Nrf2/ARE pathway, increased MT-1A, MT-1E, and MT-2A mRNA levels, and induced metallothionein proteins. These data indicated that zinc complexes may be excellent tools to analyze metallothionein induction in vascular endothelial cells.

引用

页码：217 / 224

页数：8

共 38 条

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