Murine cytomegalovirus employs the mixed lineage kinases family to regulate the spiral ganglion neuron cell death and hearing loss

被引：3

作者：

Li, Menghua ^{[1
,2
]}

Guo, Minyan ^{[1
,2
]}

Xu, Yice ^{[3
]}

Wu, Liyuan ^{[4
,5
]}

Chen, Mengbing ^{[6
]}

Dong, Yanfen ^{[4
]}

Zheng, Liting ^{[4
]}

Chen, Daishi ^{[1
,2
]}

Qiao, Yuehua ^{[4
]}

Ke, Zhaoyang ^{[1
,2
]}

Shi, Xi ^{[4
]}

机构：

[1] Jinan Univ, Dept Otolaryngol, Clin Med Coll 2, Shenzhen Peoples Hosp, Shenzhen 518020, Peoples R China

[2] Jinan Univ, Affiliated Hosp 1, Guangzhou 510632, Peoples R China

[3] Wuhan Univ Sci & Technol, Xiaogan Hosp, Dept Otolaryngol Head & Neck Surg, Xiaogan 432000, Peoples R China

[4] Xuzhou Med Univ, Artificial Auditory Lab Jiangsu Prov, Xuzhou 221000, Peoples R China

[5] Jiaxing Univ, Affiliated Hosp 2, Jiaxing 314000, Peoples R China

[6] Ankang Peoples Hosp, Ankang 725000, Peoples R China

来源：

NEUROSCIENCE LETTERS | 2023年 / 793卷

基金：

中国国家自然科学基金;

关键词：

Cytomegalovirus; SNHL; MLKs; Pyroptosis; Apoptosis; CHILDREN; JNK; INFECTION; APOPTOSIS;

D O I：

10.1016/j.neulet.2022.136990

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Cytomegalovirus (CMV)-induced sensorineural hearing loss (SNHL) is a worldwide epidemic. Recent studies have shown that the degree of spiral ganglion neuron (SGN) loss is correlated with hearing loss after CMV infection. We aimed to better understand the pathological mechanisms of CMV-related SGN death and to search for intervention measures. We found that both apoptosis and pyroptosis are involved in CMV-induced SGN death, which may be caused by the simultaneous activation of the p53/JNK and NLRP3/caspase-1 signaling pathways, respectively. Moreover, considering that mixed lineage kinase family (MLK1/2/3) are host restriction factors against viral infection and upstream regulators of the p53/JNK and inflammatory (including NLRP3-caspase1) signaling pathways, we further demonstrated that the MLKs inhibitor URMC-099 exhibited a protective effect against CMV-induced SGN death and hearing loss. These results indicate that MLKs signaling may be a key regulator and promising novel target for preventing apoptosis and even pyroptosis during the CMV infection of SGN cells and for treating hearing loss.

引用

页数：9