AIMS

Ischemic stroke is one of the leading causes of death worldwide. MicroRNAs (miRNAs) have been reported to be implicated in cerebral hypoxia injury and could serve as a therapeutic target. As the third gasotransmitter, hydrogen sulfide (HS) plays a critical role in hypoxia-induced injury in the central nervous system. Cystathionine β-synthase (CBS) is the main enzyme catalyzing the production of HS in brain. The objective of this study was to investigate the effect of miR-125b-5p on protecting against oxygen and glucose deprivation (OGD) injury in PC-12 cells by regulating CBS and HS generation.

RESULTS

The level of miR-125b-5p was increased in the rat MCAO model as well as OGD model in PC-12 cells. Meanwhile, CBS expression was remarkably downregulated. Overexpression of miR-125b-5p reduced CBS expression, decreased the HS generation, and deteriorated OGD injury in PC-12 cells. On the contrary, silencing miR-125b-5p protected PC-12 cells from OGD injury by upregulated CBS and HS levels. We found the protective effect of miR-125b-5p inhibition was associated with anti-oxidative and anti-apoptotic cell signaling through decreasing ROS level and reducing mitochondrial membrane potential (ΔΨm). Furthermore, the protective effect was absent when CBS was knockdown in PC-12 cells.

INNOVATION AND CONCLUSION

Our research discovered the regulation of CBS by miR-125b-5p. Besides, we provide the evidence for the therapeutic potential of miR-125b-5p inhibition for cerebral ischemia via CBS/HS pathway.