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基于网络的方法预测小鼠骨骼肌中 Hsp27 敲除靶点。

A network-based approach for predicting Hsp27 knock-out targets in mouse skeletal muscles.

机构信息

INRA, UMR1213 Herbivores, F-63122 Saint-Genès-Champanelle, France ; Clermont University, VetAgro Sup, UMR1213 Herbivores, BP 10448, F-63000, Clermont-Ferrand, France.

UMR CNRS - Blaise Pascal University 6547, F-63177 Aubière Cedex, France.

出版信息

Comput Struct Biotechnol J. 2013 Aug 14;6:e201303008. doi: 10.5936/csbj.201303008. eCollection 2013.

DOI:10.5936/csbj.201303008
PMID:24688716
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3962151/
Abstract

Thanks to genomics, we have previously identified markers of beef tenderness, and computed a bioinformatic analysis that enabled us to build an interactome in which we found Hsp27 at a crucial node. Here, we have used a network-based approach for understanding the contribution of Hsp27 to tenderness through the prediction of its interactors related to tenderness. We have revealed the direct interactors of Hsp27. The predicted partners of Hsp27 included proteins involved in different functions, e.g. members of Hsp families (Hsp20, Cryab, Hsp70a1a, and Hsp90aa1), regulators of apoptosis (Fas, Chuk, and caspase-3), translation factors (Eif4E, and Eif4G1), cytoskeletal proteins (Desmin) and antioxidants (Sod1). The abundances of 15 proteins were quantified by Western blotting in two muscles of HspB1-null mice and their controls. We observed changes in the amount of most of the Hsp27 predicted targets in mice devoid of Hsp27 mainly in the most oxidative muscle. Our study demonstrates the functional links between Hsp27 and its predicted targets. It suggests that Hsp status, apoptotic processes and protection against oxidative stress are crucial for post-mortem muscle metabolism, subsequent proteolysis, and therefore for beef tenderness.

摘要

得益于基因组学,我们之前已经确定了牛肉嫩度的标志物,并进行了计算生物信息学分析,从而构建了一个相互作用组,在其中我们在一个关键节点发现了 Hsp27。在这里,我们使用基于网络的方法来理解 Hsp27 通过预测与其嫩度相关的相互作用物对嫩度的贡献。我们揭示了 Hsp27 的直接相互作用物。Hsp27 的预测伴侣包括涉及不同功能的蛋白质,例如 Hsp 家族(Hsp20、Cryab、Hsp70a1a 和 Hsp90aa1)、细胞凋亡调节剂(Fas、Chuk 和 caspase-3)、翻译因子(Eif4E 和 Eif4G1)、细胞骨架蛋白(Desmin)和抗氧化剂(Sod1)的成员。通过 Western blot 在 HspB1 缺失小鼠及其对照的两种肌肉中定量了 15 种蛋白质的丰度。我们观察到在没有 Hsp27 的小鼠中,大多数 Hsp27 预测靶标数量发生了变化,主要是在最氧化的肌肉中。我们的研究证明了 Hsp27 与其预测靶标之间的功能联系。它表明 Hsp 状态、细胞凋亡过程和抗氧化应激保护对于死后肌肉代谢、随后的蛋白水解以及牛肉嫩度至关重要。

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引用本文的文献

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Calcium Homeostasis and Muscle Energy Metabolism Are Modified in HspB1-Null Mice.HspB1基因敲除小鼠的钙稳态和肌肉能量代谢发生改变。
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Heat shock protein-27 (HSP27) regulates STAT3 and eIF4G levels in first trimester human placenta.热休克蛋白27(HSP27)调节孕早期人胎盘组织中信号转导与转录激活因子3(STAT3)和真核生物翻译起始因子4G(eIF4G)的水平。
J Mol Histol. 2016 Dec;47(6):555-563. doi: 10.1007/s10735-016-9699-7. Epub 2016 Oct 6.
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The Invalidation of HspB1 Gene in Mouse Alters the Ultrastructural Phenotype of Muscles.

本文引用的文献

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Meat Sci. 2014 Aug;97(4):548-57. doi: 10.1016/j.meatsci.2014.03.016. Epub 2014 Apr 4.
2
Small heat shock proteins and their role in meat tenderness: a review.小分子热休克蛋白及其在肉嫩度中的作用:综述。
Meat Sci. 2014 Jan;96(1):26-40. doi: 10.1016/j.meatsci.2013.06.008. Epub 2013 Jun 16.
3
The GENOTEND chip: a new tool to analyse gene expression in muscles of beef cattle for beef quality prediction.
小鼠中HspB1基因的无效化改变了肌肉的超微结构表型。
PLoS One. 2016 Aug 11;11(8):e0158644. doi: 10.1371/journal.pone.0158644. eCollection 2016.
4
Expression Marker-Based Strategy to Improve Beef Quality.基于表达标记的提高牛肉品质策略。
ScientificWorldJournal. 2016;2016:2185323. doi: 10.1155/2016/2185323. Epub 2016 Mar 15.
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In Vitro Cell Dev Biol Anim. 2015 May;51(5):447-54. doi: 10.1007/s11626-014-9849-8. Epub 2014 Dec 9.
6
The functional landscape of Hsp27 reveals new cellular processes such as DNA repair and alternative splicing and proposes novel anticancer targets.Hsp27的功能全景揭示了诸如DNA修复和可变剪接等新的细胞过程,并提出了新的抗癌靶点。
Mol Cell Proteomics. 2014 Dec;13(12):3585-601. doi: 10.1074/mcp.M114.041228. Epub 2014 Oct 2.
GENOTEND 芯片:一种分析牛肉肌肉中基因表达的新工具,用于预测牛肉质量。
BMC Vet Res. 2012 Aug 15;8:135. doi: 10.1186/1746-6148-8-135.
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