Linezolid impair proplatelet formation by reducing mitochondrial energy metabolism in MEG-01 cells

IF 3.4 3区医学 Q1 HEMATOLOGY

Thrombosis research Pub Date : 2025-09-22 DOI:10.1016/j.thromres.2025.109498

Ya Yang , Ning Wang , Lirong Xiong , Peishu Fu , Yanping Tian , Shenglin Luo , Fengjun Sun , Peiyuan Xia

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引用次数: 0

Abstract

Background

Thrombocytopenia is a common adverse side effects of Linezolid (LZD) but the underlying mechanism remains unclear. This study aimed to analyze the mechanism of LZD induced thrombocytopenia for LZD induced thrombocytopenia.

Methods

Cells proliferation, proplatelet formation assay and platelet production were evaluated in human megakaryoblastic leukemia cell line MEG-01 or C57BL/6 mice following LZD administration. The metabolic profiles and gene expression of MEG-01 cells was subsequently analyzed using molecular and bioinformatics techniques.

Results

LZD induced a dose- and time-dependent decrease in cells proliferation and inhibited proplatelet formation. It alters metabolic pathways including central carbon metabolism as indicated by a decrease in pyruvate, ATP and GTP levels (P < 0.01). Expression of genes related to energy production and conversion and the cytoskeleton were altered, such as SLC25A21, HBB, PRR5, MYL4 and RHoE (P < 0.01). Pyruvate supplementation rescued reduced metabolites induced by LZD, increased proplatelet formation of MEG-01 cells and length of pseudopod (P < 0.05). Furthermore, pyruvate rescued the counts of megakaryocytes in bone marrow and peripheral platelets in LZD treated mice (P < 0.05).

Conclusion

LZD inhibits mitochondrial energy metabolism, resulting in proplatelet formation reduction. Pyruvate reverses LZD induced thrombocytopenia, which provide a basis for mechanistic insights of LZD induced thrombocytopenia.

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利奈唑胺通过降低MEG-01细胞的线粒体能量代谢而损害血小板前形成

背景：血小板减少是利奈唑胺（LZD）常见的不良反应，但其潜在机制尚不清楚。本研究旨在分析LZD诱导血小板减少的机制，探讨LZD诱导血小板减少的机制。方法观察LZD对人巨核母细胞白血病MEG-01和C57BL/6小鼠细胞增殖、血小板形成和血小板生成的影响。随后使用分子和生物信息学技术分析MEG-01细胞的代谢谱和基因表达。结果slzd具有剂量依赖性和时间依赖性，可降低细胞增殖，抑制血小板形成。通过丙酮酸、ATP和GTP水平的降低，它改变了代谢途径，包括中枢碳代谢（P < 0.01）。SLC25A21、HBB、PRR5、MYL4、RHoE等与能量产生、转化和细胞骨架相关的基因表达发生改变（P < 0.01）。补充丙酮酸可减少LZD诱导的代谢物，增加MEG-01细胞的前血小板形成和假足长度（P < 0.05）。此外，丙酮酸可恢复LZD治疗小鼠骨髓巨核细胞计数和外周血血小板计数（P < 0.05）。结论lzd抑制线粒体能量代谢，导致血小板前形成减少。丙酮酸逆转LZD诱导的血小板减少，为LZD诱导的血小板减少的机制研究提供了基础。

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

Thrombosis research 医学-外周血管病

CiteScore

14.60

自引率

4.00%

发文量

364

审稿时长

31 days

期刊介绍： Thrombosis Research is an international journal dedicated to the swift dissemination of new information on thrombosis, hemostasis, and vascular biology, aimed at advancing both science and clinical care. The journal publishes peer-reviewed original research, reviews, editorials, opinions, and critiques, covering both basic and clinical studies. Priority is given to research that promises novel approaches in the diagnosis, therapy, prognosis, and prevention of thrombotic and hemorrhagic diseases.