Open AccessSTK33 alleviates gentamicin‐induced ototoxicity in cochlear hair cells and House Ear Institute‐Organ of Corti 1 cells
Author(s) -
Zhou Meijuan,
Sun Gaoying,
Zhang Lili,
Zhang Guodong,
Yang Qianqian,
Yin Haiyan,
Li Hongrui,
Liu Wenwen,
Bai Xiaohui,
Li Jianfeng,
Wang Haibo
Publication year - 2018
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.13792
Subject(s) - ototoxicity , organ of corti , apoptosis , microbiology and biotechnology , hair cell , cochlea , blot , gene knockdown , chemistry , biology , biochemistry , anatomy , chemotherapy , gene , cisplatin , genetics
Serine/threonine kinase 33 ( STK 33), a member of the calcium/calmodulin‐dependent kinase ( CAMK ), plays vital roles in a wide spectrum of cell processes. The present study was designed to investigate whether STK 33 expressed in the mammalian cochlea and, if so, what effect STK 33 exerted on aminoglycoside‐induced ototoxicity in House Ear Institute‐Organ of Corti 1 ( HEI ‐ OC 1) cells. Immunofluorescence staining and western blotting were performed to investigate STK 33 expression in cochlear hair cells ( HC s) and HEI ‐ OC 1 cells with or without gentamicin treatment. CCK 8, flow cytometry, immunofluorescence staining and western blotting were employed to detect the effects of STK 33 knockdown, and/or U0126, and/or N‐acetyl‐L‐cysteine ( NAC ) on the sensitivity to gentamicin‐induced ototoxicity in HEI ‐ OC 1 cells. We found that STK 33 was expressed in both mice cochlear HC s and HEI ‐ OC 1 cells, and the expression of STK 33 was significantly decreased in cochlear HC s and HEI ‐ OC 1 cells after gentamicin exposure. STK 33 knockdown resulted in an increase in the cleaved caspase‐3 and Bax expressions as well as cell apoptosis after gentamicin damage in HEI ‐ OC 1 cells. Mechanistic studies revealed that knockdown of STK 33 led to activated mitochondrial apoptosis pathway as well as augmented reactive oxygen species ( ROS ) accumulation after gentamicin damage. Moreover, STK 33 was involved in extracellular signal‐regulated kinase 1/2 pathway in primary culture of HC s and HEI ‐ OC 1 cells in response to gentamicin insult. The findings from this work indicate that STK 33 decreases the sensitivity to the apoptosis dependent on mitochondrial apoptotic pathway by regulating ROS generation after gentamicin treatment, which provides a new potential target for protection from the aminoglycoside‐induced ototoxicity.