Arachidonic acid suppresses hepatic cell growth through ROS-mediated activation of transglutaminase.
Arachidonic acid suppresses hepatic cell growth through ROS-mediated activation of transglutaminase.
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花生四烯酸通过 ROS 介导的转谷氨酰胺酶激活抑制肝细胞生长
DOI：
10.1002/2211-5463.12511
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发表时间：
2018-10
期刊：
影响因子：
2.6
通讯作者：
Kojima S
中科院分区：
文献类型：
--
作者：
Qin XY;Lu J;Cai M;Kojima S
我们先前报道了在肝肿瘤发生过程中，促炎前体花生四烯酸（AA）的肝脏水平显著增加。在这里，我们报告了诱导的活性氧（ROS）介导的蛋白质交联酶转氨酶2（TG 2）的细胞活化在AA肝损伤中的关键作用。在肝细胞培养物中，AA剂量依赖性地抑制细胞生长，这伴随着诱导的TG 2核蓄积，如EGFP标记的TG 2过表达肝细胞所示。作用于TG2的化学抑制剂/shRNA阻止AA介导的细胞生长抑制。此外，AA引起ROS的显著产生，抗氧化剂阻断AA诱导的核TG 2活化和肝细胞生长抑制。我们认为AA介导的氧化应激和TG2转酰胺酶活性可能导致慢性肝损伤和炎症，从而成为肝细胞癌化学预防的潜在治疗靶点。
We previously reported a profound augmentation in the hepatic levels of a pro‐inflammatory precursor, arachidonic acid (AA), during liver tumorigenesis. Here, we report a critical role of the induced reactive oxygen species (ROS)‐mediated cellular activation of a protein cross‐linking enzyme, transglutaminase 2 (TG2), in liver injury by AA. In cultures of hepatic cells, AA dose‐dependently suppressed cell growth, which accompanied the induced nuclear accumulation of TG2, as demonstrated in EGFP‐tagged, TG2‐overexpressing hepatic cells. A chemical inhibitor/shRNA that acts against TG2 prevented AA‐mediated cell growth suppression. In addition, AA provoked significant production of ROS, and antioxidants blocked AA‐induced activation of nuclear TG2 and hepatic cell growth suppression. We propose that AA‐mediated oxidative stress and TG2 transamidase activity might contribute to chronic liver injury and inflammation and thereby serve as potential therapeutic targets for the chemoprevention of hepatocellular carcinoma.
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影响因子：
11.1
作者：
Qin XY;Hara M;Arner E;Kawaguchi Y;Inoue I;Tatsukawa H;Furutani Y;Nagatsuma K;Matsuura T;Wei F;Kikuchi J;Sone H;Daub C;Kawaji H;Lassmann T;Itoh M;Suzuki H;Carninci P;Hayashizaki Y;FANTOM consortium;Kokudo N;Forrest ARR;Kojima S
通讯作者：
Kojima S
影响因子：
9
作者：
Shrestha R;Tatsukawa H;Shrestha R;Ishibashi N;Matsuura T;Kagechika H;Kose S;Hitomi K;Imamoto N;Kojima S
通讯作者：
Kojima S
乙型肝炎或丙型肝炎病毒感染的肝细胞癌的液相色谱-质谱联用法研究
影响因子：
4.4
作者：
Zhou, Lina;Ding, Lili;Xu, Guowang
通讯作者：
Xu, Guowang
影响因子：
5.6
作者：
Kuo, Ting-Fang;Tatsukawa, Hideki;Kojima, Soichi
通讯作者：
Kojima, Soichi
影响因子：
64.8
作者：
Ma C;Kesarwala AH;Eggert T;Medina-Echeverz J;Kleiner DE;Jin P;Stroncek DF;Terabe M;Kapoor V;ElGindi M;Han M;Thornton AM;Zhang H;Egger M;Luo J;Felsher DW;McVicar DW;Weber A;Heikenwalder M;Greten TF
通讯作者：
Greten TF