A novel micropeptide, Slitharin, exerts cardioprotective effects in myocardial infarction.

IF 2.1 4区生物学 Q3 BIOCHEMICAL RESEARCH METHODS

PROTEOMICS – Clinical Applications Pub Date : 2024-09-01 Epub Date: 2024-03-05 DOI:10.1002/prca.202300128

Ahmed G E Ibrahim, Alessandra Ciullo, Shukuro Yamaguchi, Chang Li, Travis Antes, Xaviar Jones, Liang Li, Ramachandran Murali, Innokentiy Maslennikov, Niveda Sundararaman, Daniel Soetkamp, Eugenio Cingolani, Jennifer Van Eyk, Eduardo Marbán

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引用次数: 0

Abstract

Purpose: Micropeptides are an emerging class of proteins that play critical roles in cell signaling. Here, we describe the discovery of a novel micropeptide, dubbed slitharin (Slt), in conditioned media from Cardiosphere-derived cells (CDCs), a therapeutic cardiac stromal cell type.

Experimental design: We performed mass spectrometry of peptide-enriched fractions from the conditioned media of CDCs and a therapeutically inert cell type (human dermal fibrobasts). We then evaluated the therapeutic capacity of the candidate peptide using an in vitro model of cardiomyocyte injury and a rat model of myocardial infarction.

Results: We identified a novel 24-amino acid micropeptide (dubbed Slitharin [Slt]) with a non-canonical leucine start codon, arising from long intergenic non-coding (LINC) RNA 2099. Neonatal rat ventricular myocytes (NRVMs) exposed to Slt were protected from hypoxic injury in vitro compared to a vehicle or scrambled control. Transcriptomic analysis of cardiomyocytes exposed to Slt reveals cytoprotective capacity, putatively through regulation of stress-induced MAPK-ERK. Slt also exerted cardioprotective effects in rats with myocardial infarction as shown by reduced infarct size 48 h post-injury. Conclusions and clinical relavance: Thus, Slt is a non-coding RNA-derived micropeptide, identified in the extracellular space, with a potential cardioprotective function.

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一种新型微肽--Slitharin对心肌梗塞患者有保护心脏的作用。

目的：微肽是一类新兴的蛋白质，在细胞信号传导中发挥着关键作用。在这里，我们描述了在一种治疗性心脏基质细胞类型--心球衍生细胞（CDCs）的条件培养基中发现的一种新型微肽，命名为slitharin（Slt）：实验设计：我们对CDCs和一种治疗惰性细胞类型（人真皮纤维母细胞）的条件培养基中的多肽富集部分进行了质谱分析。然后，我们利用体外心肌细胞损伤模型和大鼠心肌梗死模型评估了候选肽的治疗能力：我们发现了一种新型的24氨基酸微肽（命名为Slitharin [Slt]），它具有一个非规范的亮氨酸起始密码子，产生于长基因间非编码（LINC）RNA 2099。与载体或加扰对照组相比，暴露于 Slt 的新生大鼠心室肌细胞（NRVMs）在体外受到保护，免受缺氧损伤。对暴露于 Slt 的心肌细胞进行的转录组分析显示了细胞保护能力，这可能是通过调节应激诱导的 MAPK-ERK 实现的。Slt 还能对心肌梗塞大鼠的心脏起到保护作用，这表现在损伤后 48 小时梗塞面积缩小。结论和临床意义：因此，Slt 是一种非编码 RNA 衍生的微肽，在细胞外空间被发现，具有潜在的心脏保护功能。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

PROTEOMICS – Clinical Applications 医学-生化研究方法

CiteScore

5.20

自引率

5.00%

发文量

审稿时长

1 months

期刊介绍： PROTEOMICS - Clinical Applications has developed into a key source of information in the field of applying proteomics to the study of human disease and translation to the clinic. With 12 issues per year, the journal will publish papers in all relevant areas including: -basic proteomic research designed to further understand the molecular mechanisms underlying dysfunction in human disease -the results of proteomic studies dedicated to the discovery and validation of diagnostic and prognostic disease biomarkers -the use of proteomics for the discovery of novel drug targets -the application of proteomics in the drug development pipeline -the use of proteomics as a component of clinical trials.