DOI: 10.1097/mao.0000000000005104 ISSN: 1531-7129

DEL-1 Attenuates Gentamycin-induced Ferroptosis and Apoptosis in Hair Cells Through AMPK/Autophagy-mediated Suppression of ER Stress

Do Su Lim, Jae Hak Ryu, Wonjun Cho, Hyeon Ji Gwon, A.M. Abd El-Aty, Jong Wook Shin, Ji Hoon Jeong, Tae Woo Jung
Show PDF Cite

Hypothesis:

Developmental endothelial locus-1 (DEL-1), a myokine, has been shown to reduce endoplasmic reticulum (ER) stress in various experimental models. This study aimed to examine the impact of DEL-1 on gentamicin (GT)-induced ototoxicity in cultured hair cell-like cells.

Background:

The long-term use of GTs for treating infections induces ER stress in the inner ear, leading to hair cell-like death and, as a result, hearing loss.

Methods:

Protein expression was measured via Western blot analysis, and cell viability, caspase 3 activity, and iron levels were assessed. Apoptotic cells were identified via TUNEL staining.

Results:

GT exposure triggered ferroptosis, apoptosis, and ER stress in HEI-OC1 cells, all of which were reversed by DEL-1 treatment. DEL-1 also promoted AMP-activated protein kinase (AMPK) phosphorylation and autophagy. Inhibition of AMPK with siRNA or 3-methyladenine (3-MA) reduced the protective effects of DEL-1 in the presence of GT.

Conclusion:

These findings suggest that DEL-1 mitigates ER stress via AMPK/autophagy signaling, reducing ferroptosis and apoptosis in GT-treated hair cell-like cells. These findings indicate that DEL-1, a muscle-secreted protein, may offer a therapeutic strategy for GT-induced hearing loss.

More from our Archive