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CDC-like kinase 3 deficiency aggravates hypoxia-induced cardiomyocyte apoptosis through AKT signaling pathway

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Abstract

Hypoxia-induced cardiomyocyte apoptosis is one major pathological change of acute myocardial infarction (AMI), but the underlying mechanism remains unexplored. CDC-like kinase 3 (CLK3) plays crucial roles in cell proliferation, migration and invasion, and nucleotide metabolism, however, the role of CLK3 in AMI, especially hypoxia-induced apoptosis, is largely unknown. The expression of CLK3 was elevated in mouse myocardial infarction (MI) models and neonatal rat ventricular myocytes (NRVMs) under hypoxia. Furthermore, CLK3 knockdown significantly promoted apoptosis and inhibited NRVM survival, while CLK3 overexpression promoted NRVM survival and inhibited apoptosis under hypoxic conditions. Mechanistically, CLK3 regulated the phosphorylation status of AKT, a key player in the regulation of apoptosis. Furthermore, overexpression of AKT rescued hypoxia-induced apoptosis in NRVMs caused by CLK3 deficiency. Taken together, CLK3 deficiency promotes hypoxia-induced cardiomyocyte apoptosis through AKT signaling pathway.

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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Funding

This research was funded by Medical and Health Science and Technology Development Program of Shandong Province (202103010947), the Scientific Research Foundation of Shandong Provincial Third Hospital (Q2023001), Key R&D Program of Shandong Province, China (2019GSF108249), and Jiangxi Province Municipal Health Commission Science Technology Grant (202210097).

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Authors and Affiliations

  1. School of Medicine, Tongji University, Shanghai, 200092, China

    Xiue Ma & Bowen Lin

  2. Department of Cardiology, Ji’an Hospital, Shanghai East Hospital, Ji’an, 343000, Jiangxi, China

    Liming Gao

  3. Shandong Provincial Third Hospital, Shandong University, Jinan, 250012, Shandong, China

    Rucun Ge & Lixiao Zhen

  4. Department of Cardiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201620, China

    Tianyou Yuan

Authors
  1. Xiue Ma
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  2. Liming Gao
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  3. Rucun Ge
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  4. Tianyou Yuan
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  5. Bowen Lin
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  6. Lixiao Zhen
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Contributions

Lixiao Zhen, Bowen Lin, and Tianyou Yuan conceived and designed experiments. Xiue Ma, Liming Gao and and Rucun Ge performed experiments, analyzed data, and prepared figures. Xiue Ma made the original draft preparation. Bowen Lin revised the manuscript. All authors have read and agreed to the published version of the manuscript.

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Correspondence to Tianyou Yuan, Bowen Lin or Lixiao Zhen.

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Ma, X., Gao, L., Ge, R. et al. CDC-like kinase 3 deficiency aggravates hypoxia-induced cardiomyocyte apoptosis through AKT signaling pathway. In Vitro Cell.Dev.Biol.-Animal (2024). https://doi.org/10.1007/s11626-024-00886-3

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