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

• Published in: Nitric oxide 2018-08, Vol.78, p.11-21
• Main Authors: Shen, Yaqi, Shen, Zhuqing, Guo, Lingyan, Zhang, Qiuyan, Wang, Zhijun, Miao, Lei, Wang, Minjun, Wu, Jian, Guo, Wei, Zhu, Yizhun
• Format: Article
• Language: English
• Subjects: Cystathionine β-synthase; Hydrogen sulfide; Ischemia; miRNA
• ISSN: 1089-8603; 1089-8611
• DOI: 10.1016/j.niox.2018.05.004

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. 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. 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. [Display omitted] •MiR-125-5p was able to regulate H2S production in PC-12 cells by directly targeting CBS.•MiR-125-5p inhibition contributes to protection against cerebral ischemia in vitro.•A new molecular control mechanism for endogenous H2S production in the nerve cells at the microRNA level is revealed.•This work may provide a new potential therapeutic target for cerebral ischemia via CBS/H2S pathway.