2. Academic Validation
  3. Sphingosylphosphorylcholine alleviates hypoxia-caused apoptosis in cardiac myofibroblasts via CaM/p38/STAT3 pathway

Sphingosylphosphorylcholine alleviates hypoxia-caused apoptosis in cardiac myofibroblasts via CaM/p38/STAT3 pathway

  • Apoptosis. 2020 Dec;25(11-12):853-863. doi: 10.1007/s10495-020-01639-9.
Ying Li 1 2 3,  Qi Qi 1,  Wan-Cheng Yang 1,  Tian-Liang Zhang 4,  Chen-Chen Lu 1,  Yu-Juan Yao 1,  Wei-Hua Kong 5,  Jing Zhao 6
Affiliations

Affiliations

  • 1 Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Science, Shandong University, Jinan, China.
  • 2 Research Center for Translational Medicine, Jinan Central Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.
  • 3 Research Center for Translational Medicine, Central Hospital Affiliated to Shandong First Medical University, Jinan, China.
  • 4 Experimental Center for Medical Research, Weifang Medical University, Weifang, China.
  • 5 Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Science, Shandong University, Jinan, China. whkong@sdu.edu.cn.
  • 6 Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Science, Shandong University, Jinan, China. jingzhao@sdu.edu.cn.
PMID: 33068199 DOI: 10.1007/s10495-020-01639-9
Abstract

Blockade of hypoxia-caused nonmyocytes Apoptosis helps improve survival and mitigate ventricular remodeling and dysfunction during the chronic stage of myocardial infarction. But tools affecting nonmyocyte Apoptosis are very rare. Sphingosylphosphorylcholine (SPC), a naturally occurring bioactive sphingolipid in plasma, was proved to protect cardiomyocyte against Apoptosis in an ischemic model in our previous study. Here, we showed that SPC also inhibited hypoxia-induced Apoptosis in myofibroblasts, an important type of nonmyocytes in the heart. Calmodulin (CaM) is an identified receptor of SPC. We clarified that SPC inhibited myofibroblast Apoptosis through CaM as evidenced by decreased cleaved Caspase 3, PARP1 and condensed nucleus. Furthermore, the employment of inhibitor and agonist of p38 and STAT3 suggests that SPC inhibits myofibroblast Apoptosis by regulating the phosphorylation of p38 and STAT3, and they act as downstream of CaM. The present work may provide new evidence on the regulation of myofibroblasts Apoptosis by SPC and a novel target for heart remodeling after hypoxia.

Keywords

Apoptosis; Calmodulin; Hypoxia; Myofibroblasts; STAT3; p38.

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