Lysine-specific demethylase 1 inhibitors protect cochlear spiral ganglion neurons against cisplatin-induced damage.

Abstract:

:Cisplatin is a widely used chemotherapeutic drug, but one of its side effects is ototoxicity. Epigenetic-related drugs, such as lysine-specific demethylase 1 (LSD1) inhibitors, have been reported to protect against cisplatin-induced hair cell loss by preventing demethylation of histone H3K4 (H3K4me2). However, the protective effect of LSD1 inhibitors in spiral ganglion neurons (SGNs) remains unclear. To investigate whether LSD1 inhibitors exert similar protective effects on SGNs, we treated mouse cochlear explant cultures with LSD1 inhibitors (2PCPA, S2101, or CBB1007) together with cisplatin. Low concentrations of cisplatin damaged SGNs much more than high concentrations, and blocking the demethylation of H3K4me2 with LSD1 inhibitors prevented the SGNs from injury. Reactive oxygen species are also involved in the injury process, and LSD1 inhibitors protected SGNs by increasing the expression level of the antioxidant gene Slc7a11 and decreasing the level of the pro-oxidant gene lactoperoxidase (Lpo). Our findings show that LSD1 inhibitors prevent cisplatin-induced SGN loss by regulating the demethylation of H3K4 and preventing increases of reactive oxygen species levels, which might provide a potential therapeutic strategy for cisplatin-induced hearing loss.

journal_name

Neuroreport

journal_title

Neuroreport

authors

Li A,He Y,Sun S,Cai C,Li H

doi

10.1097/WNR.0000000000000386

subject

Has Abstract

pub_date

2015-06-17 00:00:00

pages

539-47

issue

9

eissn

0959-4965

issn

1473-558X

pii

00001756-201506020-00009

journal_volume

26

pub_type

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