Oxycodone relieves permeability damage and apoptosis of oxygen-glucose deprivation/reoxygenation-induced brain microvascular endothelial cells through ras homolog family member A (RhoA)/ Rho-associated coiled-coil containing kinases (ROCK)/ myosin light chain 2 (MLC2) signal.

Abstract

Cerebrovascular disease, an important cause of acute ischemic stroke, has attracted worldwide attention. Oxycodone has been widely used to treat various painful disorders. This study was designed to explore the mechanism of oxycodone in oxygen-glucose deprivation/reoxygenation (OGD/R)-induced brain microvascular endothelial cell model. For the reliability of the results in the following experiments, the viability was firstly detected using CCK-8. With the application of LDH, TEER and TUNEL assays, the LDH expression, permeability and apoptosis of brain microvascular endothelial cells were detected, respectively. Besides, the mRNA and protein expressions of tight junction proteins and RhoA were measured using RT-qPCR and Western blot. Moreover, RT-qPCR was employed to evaluate the expressions of inflammatory cytokines. Western blot was adopted to measure the levels of RhoA, ROCK, MLC2 and apoptosis-related proteins. The results revealed that oxycodone attenuated permeability damage, inflammatory factor release and apoptosis of OGD/R-induced brain microvascular endothelial cells in a dose-dependent manner. It was also found that oxycodone could reduce the expressions of RhoA, ROCK and MLC2 in brain microvascular endothelial cells induced by OGD/R. More importantly, oxycodone exhibited desirable effects on OGD/R-induced brain microvascular endothelial cells through RhoA/ROCK/MLC2 signal. In conclusion, oxycodone relieved permeability damage and apoptosis of OGD/R-induced brain microvascular endothelial cells through RhoA/ROCK/MLC2 signal, suggesting that oxycodone might be an effective method for the improvement of cerebral ischemia-reperfusion injury.

• Authors: Fang Shao, Dong Han, Yihui Shen, Wen Bian, Liting Zou, Yiqian Hu, Wei Sun
• Journal: Bioengineered (Bioengineered) Vol. 13 Issue 3 Pg. 5205-5215 (03 2022) ISSN: 2165-5987 [Electronic] United States
• PMID: 35170371 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Myosin Light Chains
• myosin light chain 2
• RHOA protein, human
• Oxycodone
• rho-Associated Kinases
• Cardiac Myosins
• rhoA GTP-Binding Protein
• Glucose
• Oxygen

Topics

• Apoptosis
• Brain (metabolism)
• Cardiac Myosins
• Endothelial Cells (metabolism)
• Glucose (metabolism)
• Humans
• Ischemic Stroke
• Myosin Light Chains
• Oxycodone (metabolism, pharmacology)
• Oxygen (pharmacology)
• Permeability
• Reproducibility of Results
• rho-Associated Kinases (metabolism)
• rhoA GTP-Binding Protein (metabolism)