Polo-like kinase 1 promotes sepsis-induced myocardial dysfunction.

Abstract

Sepsis-induced myocardial dysfunction (SIMD) is the main cause of mortality in sepsis. In this study, we identified Polo-like kinase 1 (Plk-1) is a promoter of SIMD. Plk-1 expression was increased in lipopolysaccharide (LPS)-treated mouse hearts and neonatal rat cardiomyocytes (NRCMs). Inhibition of Plk-1 either by heterozygous deletion of Plk-1 or Plk-1 inhibitor BI 6727 alleviated LPS-induced myocardial injury, inflammation, cardiac dysfunction, and thereby improved the survival of LPS-treated mice. Plk-1 was identified as a kinase of inhibitor of kappa B kinase alpha (IKKα). Plk-1 inhibition impeded NF-κB signal pathway activation in LPS-treated mouse hearts and NRCMs. Augmented Plk-1 is thus essential for the development of SIMD and is a druggable target for SIMD.

• Authors: Zhenqiang Gao, Cuiting Zheng, Yaqi Xing, Xiyu Zhang, Yunfei Bai, Chen Chen, Yuanyuan Zheng, Wen Wang, Hongbing Zhang, Yan Meng
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 125 Issue Pt A Pg. 111074 (Dec 2023) ISSN: 1878-1705 [Electronic] Netherlands
• PMID: 37879229 (Publication Type: Journal Article)
• Copyright: Copyright © 2023 Elsevier B.V. All rights reserved.

Chemical References

• polo-like kinase 1
• NF-kappa B
• Lipopolysaccharides

Topics

• Rats
• Mice
• Animals
• Myocardium (metabolism)
• NF-kappa B (metabolism)
• Lipopolysaccharides (pharmacology)
• Cardiomyopathies (etiology, metabolism)
• Sepsis (metabolism)