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Updated: Jan 16, 2026
LC-MS Analysis of Human Platelets as a Platform for Studying Mitochondrial Metabolism
Published on: April 4, 2016
Linezolid impair proplatelet formation by reducing mitochondrial energy metabolism in MEG-01 cells
Ya Yang1, Ning Wang2, Lirong Xiong3
1Ministry 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.
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.
Insights
Linezolid (LZD) causes thrombocytopenia by inhibiting mitochondrial energy metabolism and reducing platelet production. Supplementing with pyruvate can reverse this side effect, offering a potential therapeutic strategy.
Area of Science:
- Hematology
- Pharmacology
- Cell Biology
Background:
- Thrombocytopenia is a frequent adverse effect of Linezolid (LZD).
- The precise mechanism driving LZD-induced thrombocytopenia is not fully understood.
- This study investigates the molecular mechanisms underlying LZD's impact on platelet production.
Purpose of the Study:
- To elucidate the mechanism of Linezolid (LZD)-induced thrombocytopenia.
- To investigate the role of mitochondrial energy metabolism in LZD's effects on megakaryocytes.
- To evaluate the potential of pyruvate supplementation as an intervention.
Main Methods:
- Assessed cell proliferation, proplatelet formation, and platelet production in MEG-01 cells and C57BL/6 mice.
- Analyzed metabolic profiles and gene expression in MEG-01 cells using molecular and bioinformatics approaches.
- Investigated the effects of pyruvate supplementation on LZD-treated cells and mice.
Main Results:
- Linezolid (LZD) dose-dependently decreased cell proliferation and inhibited proplatelet formation.
- LZD altered central carbon metabolism, reducing pyruvate, ATP, and GTP levels, and affected genes involved in energy production and cytoskeleton.
- Pyruvate supplementation restored metabolite levels, enhanced proplatelet formation, and rescued megakaryocyte and platelet counts in LZD-treated models.
Conclusions:
- Linezolid (LZD) impairs mitochondrial energy metabolism, leading to reduced proplatelet formation and thrombocytopenia.
- Pyruvate administration effectively reverses LZD-induced thrombocytopenia in vitro and in vivo.
- These findings provide mechanistic insights into LZD-induced thrombocytopenia and suggest pyruvate as a potential counteracting agent.
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