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Biochem Biophys Res Commun. 2018 Sep 5;503(2):665-670. doi: 10.1016/j.bbrc.2018.06.058. Epub 2018 Jun 18.

MIF protects against oxygen-glucose deprivation-induced ototoxicity in HEI-OC1 cochlear cells by enhancement of Akt-Nrf2-HO-1 pathway.

Author information

1
Department of Otolaryngology Head and Neck Surgery, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huaian, 223300, Jinagsu Province, China. Electronic address: zhuwyjs@163.com.
2
Department of Otolaryngology Head and Neck Surgery, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huaian, 223300, Jinagsu Province, China.

Abstract

Ischemia and oxidative stress play crucial roles in the pathophysiology of sudden sensorineural hearing loss (SSNHL). Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine and serves an important role in hearing function. The present study was designed to evaluate the effect of MIF on oxygen-glucose deprivation (OGD)-induced ototoxicity and to elucidate its molecular mechanism. In HEI-OC1 auditory cells, OGD reduced cell viability and increased supernatant lactate dehydrogenase (LDH) and MIF in a time-dependent manner. However, the reduced cell viability exerted by OGD was attenuated by antioxidant and MIF. Luciferase reporter assay demonstrated that MIF could activate NF-E2-related factor 2 (Nrf2), and real-time PCR showed increased mRNA expressions of Nrf2 and two Nrf2-responsive genes, including heme oxygenase-1 (HO-1) and NAD(P)H:quinone oxidoreductase 1 (NQO1). MIF also suppressed oxidative stress induced by OGD, as demonstrated by decreased MDA and increased GSH in cellular supernatant. Inhibition of Nrf2 using siRNA suppressed HO-1 protein expression, the protective effect on OGD-induced injury and decrease in oxidative stress by MIF. Moreover, MIF prevented OGD-induced reduction of Akt1 phosphorylation at Ser473. LY294002, an inhibitor of PI3K/Akt signaling, attenuated the enhancement of Nrf2 protein and protective effect of MIF in OGD-treated cochlear cells. We demonstrate that MIF protects cochlear cells against OGD-induced injury through activation of Akt-Nrf2-HO-1 pathway.

KEYWORDS:

Cochlear cell; Macrophage migration inhibitory factor (MIF); NF-E2-related factor 2 (Nrf2); Oxidative stress; Oxygen-glucose deprivation (OGD)

PMID:
29908183
DOI:
10.1016/j.bbrc.2018.06.058
[Indexed for MEDLINE]

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