MicroRNA-26b/PTEN Signaling Pathway Mediates Glycine-Induced Neuroprotection in SAH Injury.

Abstract

Subarachnoid hemorrhage (SAH) is a form of stroke associated with high mortality and morbidity. Despite advances in treatment for SAH, the prognosis remains poor. We have previously demonstrated that glycine, a non-essential amino acid is involved in neuroprotection following intracerebral hemorrhage via the Phosphatase and tensin homolog (PTEN)/protein kinase B (AKT) signaling pathway. However, whether it has a role in inducing neuroprotection in SAH is not known. The present study was designed to investigate the role of glycine in SAH. In this study, we show that glycine can reduce brain edema and protect neurons in SAH via a novel pathway. Following a hemorrhagic episode, there is evidence of downregulation of S473 phosphorylation of AKT (p-AKT), and this can be reversed with glycine treatment. We also found that administration of glycine can reduce neuronal cell death in SAH by activating the AKT pathway. Glycine was shown to upregulate miRNA-26b, which led to PTEN downregulation followed by AKT activation, resulting in inhibition of neuronal death. Inhibition of miRNA-26b, PTEN or AKT activation suppressed the neuroprotective effects of glycine. Glycine treatment also suppressed SAH-induced M1 microglial polarization and thereby inflammation. Taken together, we conclude that glycine has neuroprotective effects in SAH and is mediated by the miRNA-26b/PTEN/AKT signaling pathway, which may be a therapeutic target for treatment of SAH injury.

• Authors: Xingping Qin, Farhana Akter, Lingxia Qin, Qiurong Xie, Xinyu Liao, Rui Liu, Xueting Wu, Nina Cheng, Lingmin Shao, Xiaoxing Xiong, Renzhong Liu, Qi Wan, Songlin Wu
• Journal: Neurochemical research (Neurochem Res) Vol. 44 Issue 11 Pg. 2658-2669 (Nov 2019) ISSN: 1573-6903 [Electronic] United States
• PMID: 31612303 (Publication Type: Journal Article)

Chemical References

• MIRN26 microRNA, rat
• MicroRNAs
• Neuroprotective Agents
• PTEN Phosphohydrolase
• Pten protein, rat
• Glycine

Topics

• Animals
• Brain (pathology)
• Cell Line, Tumor
• Glycine (pharmacology)
• Humans
• Male
• MicroRNAs (physiology)
• Neuroprotective Agents (pharmacology)
• PTEN Phosphohydrolase (physiology)
• Rats, Sprague-Dawley
• Signal Transduction (physiology)
• Subarachnoid Hemorrhage (pathology, physiopathology)