NLRX1 accelerates cisplatin-induced ototoxity in HEI-OC1 cells via promoting generation of ROS and activation of JNK signaling pathway

作者

Yin, HY;Sun, GY;Yang, QQ;Chen, C;Qi, Q;Wang, HB;Li, JF

作者单位

[Yin, Haiyan; Sun, Gaoying; Yang, Qianqian; Chen, Chen; Qi, Qi; Wang, Haibo; Li, Jianfeng] Shandong Univ, Shandong Prov Hosp, Dept Otolaryngol Head & Neck Surg, Jinan 250021, Peoples R China.;-;[Yin, Haiyan; Yang, Qianqian; Chen, Chen; Qi, Qi; Li, Jianfeng] Shandong Univ, Dept Pathol & Pathophysiol, Cheeloo Hlth Sci Ctr, Jinan 250012, Peoples R China.;-;[Sun, Gaoying; Wang, Haibo; Li, Jianfeng] Shandong Prov Key Lab Otol, Jinan 250021, Peoples R China.

摘要

Nucleotide-binding domain and leucine-rich-repeat-containing family member X1 (NLRX1), located in mitochondria, can recognize cytoplasmic pattern recognition receptors and is tightly related to reactive oxygen species (ROS) production, mitochondrial function, apoptosis and inflammation. The present study was designed to explore whether NLRX1 expresses in HEI-OC1 cells and, if so, to investigate the possible correlations between NLRX1 and cisplatin-induced ototoxity in vitro. Here, we report that NLRX1 was specifically localized to mitochondria in the cytoplasm of HEI-OC1 cells and its expression was increased concurrent with the increase of ROS production and occurrence of apoptosis in HEI-OC1 cells in response to cisplatin stimulus. NLRX1 overexpression led to a higher apoptosis in HEI-OC1 cells treated with cisplatin, whereas, NLRX silencing decreased cisplatin induced apoptosis. Mechanistic studies showed that NLRX1 activated mitochondrial apoptosis pathway as well as promoted ROS generation and JNK activation. Either inhibition of ROS generation or JNK signaling significantly prevented NLRX1-mediated mitochondrial apoptosis in HEI-OC1cells. In addition, NLRX1 expression was confirmed in cochlear explants. The findings from this work reveal that NLRX1 sensitizes HEI-OC1 cells to cisplatin-induced apoptosis via activation of ROS/JNK signaling pathway, suggesting that NLRX1 acts as an important regulator of the cisplatin-elicited ototoxity.

关键词

JUNCTIONAL INTERCELLULAR COMMUNICATION; OXYGEN SPECIES PRODUCTION; REACTIVE OXYGEN; AUDITORY CELLS; INDUCED APOPTOSIS; HAIR-CELLS; IN-VITRO; INFLAMMATORY CYTOKINES; HEARING-LOSS; C-JUN

基本信息

所属机构:

归属医师: 李建峰王海波

PMID：28287190

UT：000396258300001

刊名:SCIENTIFIC REPORTS

年，卷(期):2017年7卷

DOI：10.1038/srep44311

附件： pdf

收录: SCIE