Dexmedetomidine Attenuates Hypoxia/Reoxygenation Injury of H9C2 Myocardial Cells by Upregulating miR-146a Expression via the MAPK Signal Pathway.

Abstract

INTRODUCTION AND OBJECTIVE:

Dexmedetomidine (Dex) and a number of miRNAs contribute to ischemia/reperfusion injury. We aimed to explore the role of Dex and miR-146a on myocardial cells injured by hypoxia/reoxygenation (H/R).

METHOD:

H9C2 cells were injured by H/R. Cell viability was tested using the cell counting kit-8. Lactate dehydrogenase (LDH) activity, superoxide dismutase (SOD) activity, and malondialdehyde (MDA) levels were determined using commercial kits. Flow cytometry was performed to determine apoptosis rate and reactive oxygen species (ROS) level. Protein and mRNA levels were assessed using Western blot and qPCR.

RESULTS:

miR-146a expression and cell viability of H9C2 cells were downregulated under the circumstance of H/R injury. The tendency could be reversed by Dex, which could also upregulate SOD activity and decrease apoptosis, LDH activity, MDA, 78-kDa glucose-regulated protein (GRP78), and C/EBP homologous protein (CHOP) levels of H9C2 cells. GRP78, CHOP levels, and cell viability were negatively modulated by miR-146a. Dex elevated cell viability, catalase, MnSOD, and NAD(P)H dehydrogenase (NQO1) levels but suppressed apoptosis rate, GRP78, and CHOP levels by increasing miR-146a expression and downregulating ROS, phosphorylation of p38, and extracellular signal-regulated kinases 1/2 levels. By using SB203580 (SB), the p38 mitogen-activated protein kinase (MAPK) inhibitor, Dex or the inhibition of miR-146 upregulated cell viability but downregulated GRP78 and CHOP levels.

CONCLUSION:

Dex might regulate miR-146a expression, which could further modulate the endoplasmic reticulum stress and oxidative stress and eventually affect the cell viability and apoptosis of myocardial cells injured by H/R via the MAPK signal pathway.

• Authors: Yi Chu, Jiwei Teng, Pin Feng, Hui Liu, Fangfang Wang, Haiyan Wang
• Journal: Pharmacology (Pharmacology) Vol. 107 Issue 1-2 Pg. 14-27 ( 2022) ISSN: 1423-0313 [Electronic] Switzerland
• PMID: 34718238 (Publication Type: Journal Article)
• Copyright: © 2021 S. Karger AG, Basel.

Chemical References

• Cardiotonic Agents
• MIRN146a microRNA, rat
• MicroRNAs
• Reactive Oxygen Species
• Dexmedetomidine
• Mapk1 protein, rat
• Mitogen-Activated Protein Kinase 1
• Mitogen-Activated Protein Kinase 3
• p38 Mitogen-Activated Protein Kinases

Topics

• Animals
• Apoptosis (drug effects)
• Cardiotonic Agents (pharmacology)
• Cell Hypoxia
• Cell Line
• Cell Survival (drug effects)
• Dexmedetomidine (pharmacology)
• Endoplasmic Reticulum Stress (drug effects)
• MAP Kinase Signaling System (drug effects)
• MicroRNAs (antagonists & inhibitors, genetics, metabolism)
• Mitogen-Activated Protein Kinase 1 (genetics, metabolism)
• Mitogen-Activated Protein Kinase 3 (genetics, metabolism)
• Myocardial Reperfusion Injury (drug therapy, metabolism)
• Oxidative Stress (drug effects)
• Rats
• Reactive Oxygen Species (metabolism)
• Up-Regulation (drug effects)
• p38 Mitogen-Activated Protein Kinases (antagonists & inhibitors, metabolism)