Studies on the mechanism of functional food components at molecular basis focusing on phosphorylation hub protein.

以磷酸化枢纽蛋白为重点的功能性食品成分分子基础机制研究。

• 批准号: 21580157
• 负责人: SEKI Taiichiro
• 金额: $ 3.16万
• 依托单位: Nihon University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21580157/
• 关键词: 食品機能; garlic; apoptosis; heat shock protein; Sulfide; Food function; MAPK; food function

Consumption of a certain amount of vegetables and fruits negatively correlates with the incidence of life-style related diseases including cancer. To clarify the anti-cancer effect of phytochemicals derived from vegetables and fruits at molecular basis, we focused on phosphorylation-hub protein which converts various intracellular stimuli into the phosphorylation signals. Apoptosis signal-regulating kinase 1(ASK1), a typical phosphorylation hub protein locating at the up-stream of stress-responsible kinase, SAPK/JNK, converts the intracellular stimuli to phosphorylation signals ; ASK1 is also a sort of MAPKK. In the quiescent cells, intracellular ASK1 binds with thioredoxin(Trx) to inactivate its biological activity ; oxidation of cysteine residues in Trx causes the activation of ASK1. In this study, we demonstrated for the first time that garlic derived anti-cancer compound, diallyl trisulfide, formed disulfide bond between cysteine residues in Trx molecule, followed by activation of ASK1 and formation of so-called signalsome in leukemic cells. This oxidative modification by diallyl trisulfide of the cysteine residues is a causative of apoptosi in the cells.

食用一定量的蔬菜和水果与生活方式相关疾病（包括癌症）的发病率呈负相关。为了从分子水平上阐明蔬菜和水果中植物化学物质的抗癌作用，我们将研究重点放在将细胞内各种刺激转化为磷酸化信号的磷酸化中心蛋白上。凋亡信号调节激酶1（apoptosis signal-regulating kinase 1，ASK 1）是一种典型的磷酸化枢纽蛋白，位于应激反应激酶（stress-responsible kinase，SAPK/JNK）的上游，将细胞内的刺激信号转化为磷酸化信号; ASK 1也是MAPKK的一种。在静止细胞中，细胞内的ASK 1与硫氧还蛋白（Trx）结合以抑制其生物活性; Trx中半胱氨酸残基的氧化导致ASK 1的活化。在这项研究中，我们首次证明了大蒜衍生的抗癌化合物，二烯丙基三硫化物，在Trx分子中的半胱氨酸残基之间形成二硫键，随后激活ASK 1并在白血病细胞中形成所谓的信号体。半胱氨酸残基的二烯丙基三硫化物的这种氧化修饰是细胞中的溶血的原因。

项目成果

Antibacterial Potential of Garlic-Derived Allicin and Its Cancellation by Sulfhydryl Compounds

• DOI: 10.1271/bbb.90096
• 发表时间: 2009-09-01
• 期刊: BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY
• 影响因子: 1.6
• 作者: Fujisawa, Hiroyuki;Watanabe, Kazuhiro;Ariga, Toyohiko
• 通讯作者: Ariga, Toyohiko

Taiichiro Seki Identification of novel molecular target of dially1 trisulfide in U937 cells

Taiichiro Seki 鉴定 U937 细胞中二烯丙基三硫化物的新分子靶标

• 发表时间: 2011
• 作者: Y.Shirahashi;H.Watanabe;H.Hayase;Shun Suda
• 通讯作者: Shun Suda

ヒト白血病細胞に対するガーリック由来香気成分diallyl trisulfideの抗がん作用について

大蒜芳香成分二烯丙基三硫化物对人白血病细胞的抗癌作用

• 发表时间: 2010
• 作者: 高橋伸一郎;竹中麻子;豊島由香;木村久美;加藤久典;福嶋俊明;山中大介;伯野史彦;南史朗;岩下光利;一柳孝司;田中友紀
• 通讯作者: 田中友紀

Diallyl Trisulfide Protects Rats from Carbon Tetrachloride-Induced Liver Injury

• DOI: 10.3945/jn.109.109611
• 发表时间: 2009-12-01
• 期刊: JOURNAL OF NUTRITION
• 影响因子: 4.2
• 作者: Hosono-Fukao, Tomomi;Hosono, Takashi;Ariga, Toyohiko
• 通讯作者: Ariga, Toyohiko

Anticancer effect of sulfur-containing compounds derived from garlic

大蒜含硫化合物的抗癌作用

• 发表时间: 2011
• 作者: Koizumi K;Iwasaki Y;Narukawa M;Iitsuka Y;Fukao T;Seki T;Ariga T;Watanabe T.;高須賀由佳;Koizumi K;比江森美樹;Hosono-Fukao T;Taiichiro Seki
• 通讯作者: Taiichiro Seki