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MiR-125b-5p is involved in oxygen and glucose deprivation injury in PC-12 cells via CBS/H 2 S pathway
- Source :
- Nitric Oxide. 78:11-21
- Publication Year :
- 2018
- Publisher :
- Elsevier BV, 2018.
-
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.
- Subjects :
- 0301 basic medicine
Cancer Research
Gene knockdown
Cell signaling
biology
Physiology
Chemistry
Clinical Biochemistry
Central nervous system
Ischemia
Cerebral hypoxia
medicine.disease
Biochemistry
Cystathionine beta synthase
Cell biology
03 medical and health sciences
030104 developmental biology
medicine.anatomical_structure
Downregulation and upregulation
medicine
biology.protein
Gene silencing
Subjects
Details
- ISSN :
- 10898603
- Volume :
- 78
- Database :
- OpenAIRE
- Journal :
- Nitric Oxide
- Accession number :
- edsair.doi...........1fda28c33b3ce232f9401c823a40de15