2. Academic Validation
  3. Linezolid impair proplatelet formation by reducing mitochondrial energy metabolism in MEG-01 cells

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

  • Thromb Res. 2025 Sep 22:255:109498. doi: 10.1016/j.thromres.2025.109498.
Ya Yang 1,  Ning Wang 2,  Lirong Xiong 3,  Peishu Fu 3,  Yanping Tian 4,  Shenglin Luo 5,  Fengjun Sun 6,  Peiyuan Xia 7
Affiliations

Affiliations

  • 1 Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, Department of Pharmacy, National Clinical Research Center for Child Health and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, 401122, China; Department of Pharmacy, The First Affiliated Hospital of Army Medical University, Chongqing, 400038, China.
  • 2 Department of Pharmacy, The First Affiliated Hospital of Army Medical University, Chongqing, 400038, China; Department of Cardiovascular and Respiratory Medicine, 952 Army Hospital of the PLA, Geermu, Qinghai Province, 816000, China.
  • 3 Department of Pharmacy, The First Affiliated Hospital of Army Medical University, Chongqing, 400038, China.
  • 4 Laboratory of Stem Cell and Developmental Biology, Department of Histology and Embryology, College of Basic Medical Science, Army Medical University, Chongqing, 400038, China.
  • 5 Institute of Combined Injury, State Key Laboratory of Trauma, Burns and Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Army Medical University, Chongqing, 400038, China.
  • 6 Department of Pharmacy, The First Affiliated Hospital of Army Medical University, Chongqing, 400038, China. Electronic address: fengj_sun@163.com.
  • 7 Department of Pharmacy, The First Affiliated Hospital of Army Medical University, Chongqing, 400038, China. Electronic address: peiyuan_xia@tmmu.edu.cn.
PMID: 41005026 DOI: 10.1016/j.thromres.2025.109498
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.

Keywords

Energy metabolism; Linezolid; Proplatelet; Pyruvate; Thrombocytopenia.

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