Open Access

ARTICLE

Dexmedetomidine alleviates oxygen and glucose deprivation-induced apoptosis in mesenchymal stem cell via downregulation of MKP-1

RUICONG GUAN1,3,#, KUAN ZENG1,#, MINNAN GAO1, JIANFEN LI1, HUIQI JIANG1, LU ZHANG1, JINGWEN LI1, BIN ZHANG1, YUQIANG LIU1, ZHUXUAN LIU1, DIAN WANG1, YANQI YANG1,2,*
1 Department of Cardiovascular Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
2 Department of Cardiothoracic Surgery, University Hospital, Linköping University, Linköping, Sweden
3 Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
* Corresponding Author: YANQI YANG. Email:

BIOCELL 2022, 46(11), 2455-2463. https://doi.org/10.32604/biocell.2022.021661

Received 26 January 2022; Accepted 18 April 2022; Issue published 07 July 2022

Abstract

Bone marrow mesenchymal stem cell (MSC)-based therapy is a novel candidate for heart repair. But ischemia-reperfusion injury leads to low viability of MSC. Dexmedetomidine (Dex) has been found to protect neurons against ischemia-reperfusion injury. It remains unknown if Dex could increase the viability of MSCs under ischemia. The present study is to observe the potential protective effect of Dex on MSCs under ischemia and its underlying mechanisms. Specific mRNAs related to myocardial ischemia in the GEO database were selected from the mRNA profiles assessed in a previous study using microarray. The most dysregulated mRNAs of the specific ones from the above study were subject to bioinformatics analysis at our laboratory. These dysregulated mRNAs possibly regulated apoptosis of cardiomyocytes and were validated in vitro for their protective effect on MSCs under ischemia. MSCs were pre-treated with Dex at 10 μM concentration for 24 h under oxygen-glucose deprivation (OGD). Flow cytometry and TUNEL assay were carried out to detect apoptosis in Dex-pretreated MSCs under OGD. The relative expressions of mitogen-activated protein kinase phosphatase 1 (MKP-1) and related genes were detected by quantitative polymerase chain reaction and western blotting. Microarray data analysis revealed that Dex regulates MAPK phosphatase activity. Dex significantly reduced in vitro apoptosis of MSCs under OGD, which suppressed the synthesis level of Beclin1 and light chain 3 proteins. Dex down-regulated MKP-1 expression and attenuated an OGD-induced change in the mitogen activated protein kinase 3 (MAPK3) signaling pathway. Dex increases the viability of MSC and improves its tolerance to OGD in association with the MKP-1 signaling pathway, thus suggesting the potential of Dex as a novel strategy for promoting MSCs efficacy under ischemia.

Keywords

Dexmedetomidine; HIF-1α; MKP-1; Oxygen and glucose deprivation

Cite This Article

GUAN, R., ZENG, K., GAO, M., LI, J., JIANG, H. et al. (2022). Dexmedetomidine alleviates oxygen and glucose deprivation-induced apoptosis in mesenchymal stem cell via downregulation of MKP-1. BIOCELL, 46(11), 2455–2463.



This work is licensed under a Creative Commons Attribution 4.0 International License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
  • 380

    View

  • 198

    Download

  • 0

    Like

Share Link

WeChat scan