Proteomics and phosphoproteomics study of LCMT1 overexpression and oxidative stress: overexpression of LCMT1 arrests H2O2-induced lose of cells viability.

IF 5.2 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Redox Report Pub Date : 2019-12-01 DOI:10.1080/13510002.2019.1595332
Xinhang Wang, Shen Tang, Fu Qin, Yuyang Liu, Ziwei Liang, Haiqing Cai, Laiming Mo, Deqiang Xiao, Songcao Guo, Yiqiang Ouyang, Bin Sun, Cailing Lu, Xiyi Li
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引用次数: 8

Abstract

Objectives: Protein phosphatase 2A (PP2A), a major serine/threonine phosphatase, is also known to be a target of ROS. The methylation of PP2A can be catalyzed by leucine carboxyl methyltransferase-1 (LCMT1), which regulates PP2A activity and substrate specificity.

Methods: In the previous study, we have showed that LCMT1-dependent PP2Ac methylation arrests H2O2-induced cell oxidative stress damage. To explore the possible protective mechanism, we performed iTRAQ-based comparative quantitative proteomics and phosphoproteomics studies of H2O2-treated vector control and LCMT1-overexpressing cells.

Results: A total of 4480 non-redundant proteins and 3801 unique phosphopeptides were identified by this means. By comparing the H2O2-regulated proteins in LCMT1-overexpressing and vector control cells, we found that these differences were mainly related to protein phosphorylation, gene expression, protein maturation, the cytoskeleton and cell division. Further investigation of LCMT1 overexpression-specific regulated proteins under H2O2 treatment supported the idea that LCMT1 overexpression induced ageneral dephosphorylation of proteins and indicated increased expression of non-erythrocytic hemoglobin, inactivation of MAPK3 and regulation of proteins related to Rho signal transduction, which were known to be linked to the regulation of the cytoskeleton.

Discussion: These data provide proteomics and phosphoproteomics insights into the association of LCMT1-dependent PP2Ac methylation and oxidative stress and indirectly indicate that the methylation of PP2A plays an important role against oxidative stress.

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LCMT1过表达与氧化应激的蛋白质组学和磷酸化蛋白质组学研究:LCMT1过表达可阻止h2o2诱导的细胞活力丧失。
目的:蛋白磷酸酶2A (PP2A)是一种主要的丝氨酸/苏氨酸磷酸酶,也是已知的ROS的靶标。亮氨酸羧基甲基转移酶-1 (leucine carboxyl methyltransferase-1, LCMT1)可以催化PP2A的甲基化,调节PP2A的活性和底物特异性。方法:在之前的研究中,我们已经证明lcmt1依赖性PP2Ac甲基化可以抑制h2o2诱导的细胞氧化应激损伤。为了探索可能的保护机制,我们对h2o2处理的载体对照和lcmt1过表达的细胞进行了基于itraq的比较定量蛋白质组学和磷酸化蛋白质组学研究。结果:共鉴定出4480个非冗余蛋白和3801个独特的磷酸肽。通过比较lcmt1过表达细胞和载体对照细胞中h2o2调控的蛋白,我们发现这些差异主要与蛋白磷酸化、基因表达、蛋白成熟、细胞骨架和细胞分裂有关。对H2O2处理下LCMT1过表达特异性调控蛋白的进一步研究支持了LCMT1过表达诱导蛋白普遍去磷酸化的观点,并表明非红细胞血红蛋白表达增加、MAPK3失活和Rho信号转导相关蛋白的调控,这些蛋白已知与细胞骨架的调控有关。讨论:这些数据为lcmt1依赖性PP2Ac甲基化与氧化应激的关联提供了蛋白质组学和磷酸化蛋白质组学的见解,并间接表明PP2A甲基化在抗氧化应激中起重要作用。
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来源期刊
Redox Report
Redox Report 生物-生化与分子生物学
CiteScore
6.10
自引率
0.00%
发文量
28
审稿时长
>12 weeks
期刊介绍: Redox Report is a multidisciplinary peer-reviewed open access journal focusing on the role of free radicals, oxidative stress, activated oxygen, perioxidative and redox processes, primarily in the human environment and human pathology. Relevant papers on the animal and plant environment, biology and pathology will also be included. While emphasis is placed upon methodological and intellectual advances underpinned by new data, the journal offers scope for review, hypotheses, critiques and other forms of discussion.
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