Advanced oxidation protein products induce S-phase arrest of hepatocytes via the ROS-dependent, β-catenin-CDK2-mediated pathway.
Advanced oxidation protein products induce S-phase arrest of hepatocytes via the ROS-dependent, β-catenin-CDK2-mediated pathway.
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高级氧化蛋白产品通过 ROS 依赖性、β-连环蛋白-CDK2 介导的途径诱导肝细胞 S 期停滞
DOI：
10.1016/j.redox.2017.09.011
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发表时间：
2018-04
期刊：
影响因子：
11.4
通讯作者：
Zhou J
中科院分区：
文献类型：
--
作者：
Sun S;Xie F;Xu X;Cai Q;Zhang Q;Cui Z;Zheng Y;Zhou J
肝再生在肝部分切除术（PH）中具有重要的临床意义。PH值升高后，静止的肝细胞可以重新进入细胞周期，恢复肝脏质量。肝细胞周期进程作为肝脏再生的基本动力，可被多种病理因素如氧化应激破坏。本研究旨在评估高级氧化蛋白产物（AOPP）在肝细胞s期阻滞中的作用。测定33例肝细胞癌（HCC）围手术期血清AOPP水平。短句来源将大鼠血清白蛋白（RSA）与次氯酸孵育后制备的AOPP作用于正常大鼠、人和小鼠肝细胞系HL-7702和AML-12，研究AOPP对肝细胞周期进程和肝再生的影响。AOPP治疗损害了70%肝部分切除大鼠的肝再生。AOPP可诱导大鼠部分肝切除术后残余肝细胞以及HL-7702和AML-12细胞的s期阻滞。AOPP对肝细胞S期阻滞的影响主要通过烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶依赖性活性氧（ROS）的产生、下游β-catenin信号的下调和细胞周期蛋白依赖性激酶2 （CDK2）表达的降低介导，从而抑制肝细胞S期进展。本研究提供了初步证据，证明AOPP可以通过ros依赖性、β-catenin- cdk2介导的途径诱导肝细胞s期阻滞。这些发现提示了AOPP对肝再生受损的一种新的致病作用，并可能为开发新的策略来改善ph患者的肝再生提供基础。在HCC患者部分肝切除术后，首次发现血清AOPP增加。静脉注射AOPP可诱导大鼠肝部分切除术后肝细胞s期骤停。aopp诱导的肝细胞s期阻滞是通过ROS-β-catenin-CDK2途径介导的。
Liver regeneration has important clinical importance in the setting of partial hepatectomy (PH). Following PH, quiescent hepatocytes can reenter cell cycle to restore liver mass. Hepatocyte cell cycle progression, as the basic motivations of liver regeneration, can be disrupted by multiple pathological factors such as oxidative stress. This study aimed to evaluate the role of advanced oxidation protein products (AOPP) in S-phase arrest in hepatocytes. Serum AOPP level were measured during the perioperative period of PH in 33 patients with hepatocellular carcinoma (HCC). Normal Sprague Dawley rats, human and murine liver cell line (HL-7702 and AML-12) were challenged with AOPP prepared by incubation of rat serum albumin (RSA) with hypochlorous acid, and the effect of AOPP on hepatocytes cell cycle progression and liver regeneration was studied after PH. AOPP levels were increased following partial hepatectomy (PH) in patients with primary liver cancer. AOPP treatment impaired liver regeneration in rats following 70% partial hepatectomy. S-phase arrest was induced by AOPP administration in hepatocytes derived from the remnant liver at controlled times following partial hepatectomy in rats, and in HL-7702 and AML-12 cells. The effect of AOPP on hepatocyte S phase arrest was mainly mediated by a nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-dependent reactive oxygen species (ROS) generation, downregulation of downstream β-catenin signaling and decreased cyclin-dependent kinase 2 (CDK2) expression, which inhibited S-phase progression in hepatocytes. This study provides preliminary evidence that AOPP can induce S-phase arrest in hepatocytes via the ROS-dependent, β-catenin-CDK2-mediated pathway. These findings suggest a novel pathogenic role of AOPP contributing to the impaired liver regeneration and may provide the basis for developing new strategies to improve liver regeneration in patients undergoing PH. Serum AOPP were first found to increase following partial hepatectomy in HCC patients. Intravenous injection of AOPP can induce hepatocytes S-phase arrest following partial hepatectomy in rats. AOPP-induced hepatocytes S-phase arrest is mediated by ROS-β-catenin-CDK2 pathway.
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影响因子：
--
作者：
Chen PM;Lin CH;Li NT;Wu YM;Lin MT;Hung SC;Yen ML
通讯作者：
Yen ML
影响因子：
25.7
作者：
Kohjima, Motoyuki;Tsai, Tsung-Huang;Tackett, Bryan C.;Thevananther, Sundararajah;Li, Lan;Chang, Benny Hung-Junn;Chan, Lawrence
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Chan, Lawrence
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5.5
作者：
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通讯作者：
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影响因子：
5.4
作者：
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通讯作者：
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影响因子：
7.4
作者：
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通讯作者：
Balestrieri, Maria Luisa