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Lipidomics Analysis Reveals a Protective Effect of Myriocin on Cerebral Ischemia/Reperfusion Model Rats

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Abstract

Ceramide accumulation has been associated with ischemic stroke. Myriocin is an effective serine palmitoyltransferase (SPT) inhibitor that reduces ceramide levels by inhibiting the de novo synthesis pathway. However, the role of myriocin in cerebral ischemia/reperfusion (I/R) injury and its underlying mechanism remain unknown. The present study established an experimental rat model of middle cerebral artery occlusion (MCAO). We employed ultra-performance liquid chromatograph quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS)–based lipidomic analysis to identify the disordered lipid metabolites and the effects of myriocin in cerebral cortical tissues of rats. In this study, we found 15 characterized lipid metabolites involved in sphingolipid and glycerophospholipid metabolism in cerebral I/R-injured rats, and these alterations were significantly alleviated by myriocin. Specifically, the mRNA expression of metabolism-related enzyme genes was detected by real-time quantitative polymerase chain reaction (RT-qPCR). We demonstrated that myriocin could regulate the mRNA expression of ASMase, NSMase, SGMS1, SGMS2, ASAH1, ACER2, and ACER3, which are involved in sphingolipid metabolism and PLA2, which is involved in glycerophospholipid metabolism. Moreover, TUNEL and Western blot assays showed that myriocin plays a key role in regulating neuronal cell apoptosis. In summary, the present work provides a new perspective for the systematic study of metabolic changes in ischemic stroke and the therapeutic applications of myriocin.

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Data Availability

The data generated during the current study are available from the corresponding author upon request.

Availability of Data and Materials

The data and materials generated during the current study are available from the corresponding author upon request.

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Funding

This work was supported by the Key Scientific Research Project in Colleges and Universities of Henan Province (Grant No.19A360033) and the Science and Technology Department of Henan Province (Grant No.182102310169, No.182102310540)—the authors are grateful to these institutions for the financial support.

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    Authors and Affiliations

    1. Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou, 450052, Henan Province, People’s Republic of China

      Ting Wang, Jingmin Zhang, Meng Yang, Jinxiu Guo, Duolu Li & Ying Li

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    1. Ting Wang
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    2. Jingmin Zhang
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    3. Meng Yang
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    4. Jinxiu Guo
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    5. Duolu Li
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    6. Ying Li
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    Contributions

    Y. L. and D. L. conceived and designed the study; T. W. performed the experiments and drafted the manuscript; J. Z. and M. Y. contributed to acquisition of data or analysis data; J. G. was responsible for editing; Y. L. and D. L. reviewed the manuscript. All authors approved the final manuscript.

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    Correspondence to Duolu Li or Ying Li.

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    The animal experiments were approved by the Institutional Animal Care and Animal Ethics Committee of Zhengzhou University.

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    Wang, T., Zhang, J., Yang, M. et al. Lipidomics Analysis Reveals a Protective Effect of Myriocin on Cerebral Ischemia/Reperfusion Model Rats. J Mol Neurosci 72, 1846–1858 (2022). https://doi.org/10.1007/s12031-022-02014-w

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