MiR-125b-5p is involved in oxygen and glucose deprivation injury in PC-12 cells via CBS/H2S pathway

Abstract

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 (H₂S) 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 H₂S 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 H₂S 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 H₂S 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 H₂S 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/H₂S pathway.

Keywords: Cystathionine β-synthase; Hydrogen sulfide; Ischemia; miRNA.