Magnesium protects mouse hippocampal HT22 cells against hypoxia-induced injury by upregulation of miR-221.

Author(s) Mi, F.; Liu, F.; Zhang, C.
Journal J Cell Biochem
Date Published 2020 Feb
Abstract

Magnesium (Mg ) has been shown to exert neuroprotective effects against hypoxia. However, it still remains elusive whether Mg protected mouse hippocampal HT22 cells against hypoxia-evoked damages. Therefore, we aimed to investigate the function of Mg and mechanisms associated with microRNA-221 (miR-221). HT22 cells were exposed to 3% O for 24 hours to induce hypoxic damages with 21% as a normoxic culture condition. The damages were monitored by viability, migration, and apoptosis of HT22 cells with or without Mg pretreatment. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was applied to examine the alteration of miR-221, miR-210, and miR-17-5p. Transduction was carried out to artificially alter the expression of miR-221 and nerve growth factor (NGF), which was confirmed by qRT-PCR or Western blot assays. To blunt phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) and nuclear factor κB (NF-κB), LY294002 (10 µM) and BAY 11-7082 (10 µM) were used. We observed Mg protected HT22 cells against hypoxia-induced damages by upregulating miR-221. Further, miR-221 positively regulated NGF expression. Overexpression of NGF alleviated cell injury, while suppression of NGF aggravated cell injury. Moreover, miR-221 elevated NGF by inducing phosphorylation of regulators in PI3K/AKT and NF-κB transduction cascades and then alleviated cell injury. In conclusion, Mg protected HT22 cells against hypoxia-induced damages by upregulation of miR-221 and NGF. These findings provided insights into the development of improved strategies for clinical application.

DOI 10.1002/jcb.29381
ISSN 1097-4644
Citation Mi F, Liu F, Zhang C. Magnesium protects mouse hippocampal HT22 cells against hypoxia-induced injury by upregulation of miR-221. J Cell Biochem. 2020;121(2):1452-1462.