A novel micropeptide, Slitharin, exerts cardioprotective effects in myocardial infarction.
A novel micropeptide, Slitharin, exerts cardioprotective effects in myocardial infarction.
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一种新型微肽 Slitharin 在心肌梗塞中发挥心脏保护作用。
DOI：
10.1002/prca.202300128
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发表时间：
2024
期刊：
影响因子：
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通讯作者：
Marbán,Eduardo
中科院分区：
文献类型：
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作者：
Ibrahim,AhmedGE;Ciullo,Alessandra;Yamaguchi,Shukuro;Li,Chang;Antes,Travis;Jones,Xaviar;Li,Liang;Murali,Ramachandran;Maslennikov,Innokentiy;Sundararaman,Niveda;Soetkamp,Daniel;Cingolani,Eugenio;VanEyk,Jennifer;Marbán,Eduardo
目的：微肽是一类在细胞信号转导中起关键作用的蛋白质。在这里，我们描述了一种新的微肽，被称为slitharin（Slt），在条件培养基中的发现，从骨髓球衍生细胞（CDCs），治疗性心脏基质细胞类型。实验设计：我们进行了质谱的肽富集馏分从条件培养基的CDCs和治疗惰性细胞类型（人皮肤成纤维细胞）。结果：我们鉴定了一种新的24-氨基酸微肽（被称为Slitharin [Slt]），它具有一个非经典的亮氨酸起始密码子，来源于长基因间非编码（LINC）RNA 2099。新生大鼠心室肌细胞（NRVMs）暴露于SLT的保护缺氧损伤在体外相比，车辆或混乱的控制。暴露于Slt的心肌细胞的转录组学分析揭示了细胞保护能力，通过调节应激诱导的MAPK-ERK来增强。Slt还在心肌梗死大鼠中发挥心脏保护作用，如在损伤后48 h梗死面积减少所示。结论和临床relavance：因此，Slt是一种非编码RNA衍生的微肽，在细胞外空间中鉴定，具有潜在的心脏保护功能。
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.