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患有肌节基因突变和肥厚型心肌病的猫的血清肽组学分析

Analysis of the Serum Peptidomics Profile for Cats With Sarcomeric Gene Mutation and Hypertrophic Cardiomyopathy.

作者信息

Sukumolanan Pratch, Phanakrop Narumon, Thaisakun Siriwan, Roytrakul Sittiruk, Petchdee Soontaree

机构信息

Veterinary Clinical Studies Program, Faculty of Veterinary Medicine, Graduated School, Kasetsart University, Nakorn Pathom, Thailand.

Functional Ingredients and Food Innovation Research Group, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Pathum Thani, Thailand.

出版信息

Front Vet Sci. 2021 Nov 8;8:771408. doi: 10.3389/fvets.2021.771408. eCollection 2021.

Abstract

Hypertrophic cardiomyopathy (HCM) has a complex phenotype that is partly explained by genetic variants related to this disease. The serum peptidome profile is a promising approach to define clinically relevant biomarkers. This study aimed to classify peptide patterns in serum samples between cats with sarcomeric gene mutations and normal cats. In the total serum samples from 31 cats, several essential proteins were identified by peptidomics analysis. The 5,946 peptides were differentially expressed in cats with sarcomeric gene mutations compared with cats without mutations. Our results demonstrated characteristic protein expression in control cats, Maine Coon cats, and Maine Coon cats with gene mutations. In cats with gene mutations, peptide expression profiling showed an association with three peptides, Cytochrome 3a132 (CYP3A132), forkhead box O1 (FOXO1), and ArfGAP, with GTPase domains, ankyrin repeats, and PH domain 2 (AGAP2). The serum peptidome of cats with mutations might provide supporting evidence for the dysregulation of metabolic and structural proteins. Genetic and peptidomics investigations may help elucidate the phenotypic variability of HCM and treatment targets to reduce morbidity and mortality of HCM in cats.

摘要

肥厚型心肌病(HCM)具有复杂的表型,部分原因可由与该疾病相关的基因变异来解释。血清肽组谱是定义临床相关生物标志物的一种有前景的方法。本研究旨在对患有肌节基因突变的猫和正常猫的血清样本中的肽模式进行分类。在来自31只猫的全血清样本中,通过肽组学分析鉴定出了几种重要蛋白质。与未发生突变的猫相比,5946种肽在患有肌节基因突变的猫中差异表达。我们的结果显示了对照猫、缅因猫和患有基因突变的缅因猫中特征性的蛋白质表达。在患有基因突变的猫中,肽表达谱显示与三种肽相关,即细胞色素3a132(CYP3A132)、叉头框O1(FOXO1)以及具有GTP酶结构域、锚蛋白重复序列和PH结构域2的ArfGAP(AGAP2)。患有突变的猫的血清肽组可能为代谢和结构蛋白的失调提供支持性证据。基因和肽组学研究可能有助于阐明HCM的表型变异性以及降低猫HCM发病率和死亡率的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a282/8606535/92980159c4f7/fvets-08-771408-g0001.jpg

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