miR-424 protects PC-12 cells from OGD-induced injury by negatively regulating MKP-1.

Abstract

OBJECTIVE:

It's of great significance to investigate the novel targets of drugs for the treatment of stroke. In this study, we explored the neuroprotective role of miR-424 in oxygen glucose deprivation (OGD)-induced injuries in PC-12 cells.

MATERIALS AND METHODS:

PC-12 cells were subjected to OGD stimulation to mimic ischemic injury. The expressions of miR-424 and mitogen-activated protein kinase phosphatase-1 (MKP-1) were altered by transient transfection with miR-424 mimic, miR-424 inhibitor, pEX-MKP-1, or sh-MKP-1. Cell counting kit-8 (CCK-8) assay, flow cytometry, and quantitative reverse transcription polymerase chain reaction (qRT-PCR), were conducted to respectively detect cell viability, apoptotic cells, and the expression of miR-424 and MKP-1. The protein expressions of several factors were determined by Western blot. Meanwhile, relative luciferase activity assay was done to verify the predicted targets association.

RESULTS:

OGD induced injury in PC-12 cells by suppressing cell viability and inducing apoptosis. OGD also induced the expression of miR-424 in PC-12 cells. Overexpression of miR-424 protected PC-12 cells from OGD-induced injury by increasing cell viability and decreasing apoptosis. MKP-1 was a direct target of miR-424, and its expression was negatively regulated by miR-424. Up-regulation of expression of MKP-1 aggravated OGD-induced cell injury by inhibiting the expression of hypoxia-inducible factor 1α (HIF-1α), thus inhibiting the PI3K/AKT/mTOR pathways.

CONCLUSIONS:

miR-424 protected PC-12 cells from OGD-induced injury through direct suppression of MKP-1 expression, as MKP-1 promoted OGD-induced cell injury by inhibiting the expression of HIF-1α and PI3K/AKT/mTOR pathways.

• Authors: Y-X Cao, Z-Q Wang, J-X Kang, K Liu, C-F Zhao, Y-X Guo, B-H Jiao
• Journal: European review for medical and pharmacological sciences (Eur Rev Med Pharmacol Sci) Vol. 22 Issue 5 Pg. 1426-1436 (03 2018) ISSN: 2284-0729 [Electronic] Italy
• PMID: 29565504 (Publication Type: Journal Article)

Chemical References

• Hypoxia-Inducible Factor 1, alpha Subunit
• MicroRNAs
• Phosphatidylinositol 3-Kinases
• Dual Specificity Phosphatase 1
• Dusp1 protein, rat
• Glucose

Topics

• Animals
• Cell Survival
• Dual Specificity Phosphatase 1 (genetics, physiology)
• Glucose (metabolism)
• Hypoxia-Inducible Factor 1, alpha Subunit (physiology)
• Hypoxia-Ischemia, Brain (prevention & control)
• MicroRNAs (physiology)
• Neuroprotection
• PC12 Cells
• Phosphatidylinositol 3-Kinases (physiology)
• Rats