Home CERKL alleviates ischemia reperfusion-induced nervous system injury through modulating the SIRT1/PINK1/Parkin pathway and mitophagy induction
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CERKL alleviates ischemia reperfusion-induced nervous system injury through modulating the SIRT1/PINK1/Parkin pathway and mitophagy induction

  • Shaoyue Huang , Zhen Hong , Leguo Zhang , Jian Guo , Yanhua Li and Kuo Li ORCID logo EMAIL logo
Published/Copyright: March 2, 2022
Biological Chemistry
From the journal Biological Chemistry Volume 403 Issue 7

Abstract

Recent studies showed that Ceramide Kinase-Like Protein (CERKL)was expressed in the nerve cells and could regulate autophagy. Sirtuin-1 (SIRT1) is the regulator of the mitophagy, which can be stabilized by CERKL. Furthermore, the study also revealed that the SIRT1 induced mitophagy by activating PINK1/Parkin signaling. Therefore, we speculated that CERKL has potential to activate the SIRT1/PINK1/Parkin pathway to induce mitophagy. In this study, cerebral ischemia reperfusion mouse model was established. CERKL was overexpressed in those mice and human neuroblastoma cells. Tunel staining and flow cytometry were applied for the detection of cell apoptosis. The ratios of LC3Ⅱ to LC3Ⅰ and the expression of LC3Ⅱ in mitochondria were determined by gel electrophoresis. Overexpression of CERKL alleviated the cerebral ischemia reperfusion injury and damage to OGD/R human neuroblastoma cells. Overexpression of CERKL enhanced the expression of LC3 Ⅱ in mitochondria and induced occurrence of mitophagy. Overexpression of CERKL promoted the stability of SIRT1 and facilitated the expression of PINK1 and Parkin in those cells. Knockdown of PINK1 impeded the mitophagy and suppressed the expression of LC3 Ⅱ in mitochondria. It can be concluded that CERKL alleviated the ischemia reperfusion induced nervous system injury through inducing mitophagy in a SIRT1/PINK1/Parkin dependent pathway.

Keywords: cerebral ischemia reperfusion; CERKL; mitophagy; SIRT1
Corresponding author: Kuo Li, Department of Neurology Cangzhou Central Hospital, No. 16 Xinhua Western Road, Cangzhou 061000, Hebei, China, E-mail:

  1. Author contributions: Shaoyue Huang and Zhen Hong designed the study, supervised the data collection, Leguo Zhang analyzed the data, interpreted the data, Jian Guo, Yanhua Li and Kuo Li prepare the manuscript for publication and reviewed the draft of the manuscript. All authors have read and approved the manuscript.

  2. Research funding: None declared.

  3. Conflict of interest statement: The authors declare no conflicts of interest regarding this article.

  4. Ethics approval: Ethical approval was obtained from the Ethics Committee of Cangzhou Central Hospital.

  5. Availability of Data and Materials: All data generated or analyzed during this study are included in this published article.

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Received: 2021-11-08
Accepted: 2022-02-16
Published Online: 2022-03-02
Published in Print: 2022-06-27

© 2022 Walter de Gruyter GmbH, Berlin/Boston

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  11. CERKL alleviates ischemia reperfusion-induced nervous system injury through modulating the SIRT1/PINK1/Parkin pathway and mitophagy induction
https://doi.org/10.1515/hsz-2021-0411
Keywords for this article
cerebral ischemia reperfusion; CERKL; mitophagy; SIRT1

Articles in the same Issue

  1. Frontmatter
  2. Review
  3. Chemerin – exploring a versatile adipokine
  4. Research Articles/Short Communications
  5. Protein Structure and Function
  6. Evolutionary adaptation of DHFR via expression of enzyme isoforms with various binding properties and dynamics behavior: a bioinformatics and computational study
  7. Cell Biology and Signaling
  8. SRPK1 promotes cell proliferation and tumor growth of osteosarcoma through activation of the NF-κB signaling pathway
  9. LINC00520 up-regulates SOX5 to promote cell proliferation and invasion by miR-4516 in human hepatocellular carcinoma
  10. Long non-coding RNA FAM66C regulates glioma growth via the miRNA/LATS1 signaling pathway
  11. CERKL alleviates ischemia reperfusion-induced nervous system injury through modulating the SIRT1/PINK1/Parkin pathway and mitophagy induction
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