3-Hydro-2,2,5,6-tetramethylpyrazine: A novel inducer of zinc transporter-1 in HepG2 human hepatocellular carcinoma cells

被引：1

作者：

Ishida, Takumi ^{[1
]}

Yamaguchi, Tadatoshi ^{[1
]}

Takechi, Shinji ^{[1
]}

机构：

[1] Sojo Univ, Fac Pharmaceut Sci, Nishi Ku, Kumamoto 8600082, Japan

来源：

ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS | 2015年 / 580卷

基金：

日本学术振兴会;

关键词：

Zinc transporter-1; Induction; Metal-responsive transcription factor 1; Oxidative stress; Glycation product; 3-Hydro-2,2,5,6-tetramethylpyrazine; TRANSCRIPTION FACTOR-I; GLYCATION END-PRODUCTS; OXIDATIVE STRESS; FACTOR MTF-1; POSSIBLE INVOLVEMENT; METALLOTHIONEIN; BINDING; DIHYDROPYRAZINES; GENE; SPECIFICITY;

D O I：

10.1016/j.abb.2015.07.002

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：

Dihydropyrazine compounds, including 3-hydro-2,2,5,6-tetramethylpyrazine (DHP-3), are low-molecular-weight glycation products spontaneously generated in vivo and also ingested via food. Our preliminary study using microarray analysis demonstrated that DHP-3 induced zinc transporter-1 (ZnT-1) in HepG2 cells. It is well known that the increase of intracellular zinc is a sensitive stimulating factor for ZnT-1 protein induction; however, there is little information about the induction of ZnT-1 by low-molecular-weight chemical compounds. Here, we attempted to clarify the mechanism of ZnT-1 induction by DHP-3. A significant increase of ZnT-1 mRNA was observed 6 h after DHP-3 treatment at concentrations over 0.5 mM, and disappeared 24 h after exposure. This induction pattern followed that of metal-responsive transcription factor 1 (MTF-1) mRNA, a metalloregulatory protein that serves as a major transcription factor of ZnT-1. Moreover, DHP-3 yielded transcriptional activation of MTF-1 in a luciferase reporter assay. The intracellular zinc content was unaffected by the compound; however, oxidative stress was observed in cells under the same conditions that activated the MTF-1 signaling pathway. These results suggest that DHP-3 is a novel ZnT-1 inducer and acts via activation of the MTF-1 signaling pathway. Additionally, the activation of MTF-1 by this compound likely occurs through oxidative stress. (C) 2015 Elsevier Inc. All rights reserved.

引用

页码：57 / 63

页数：7

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