scholarly journals Author response: Deficit of mitogen-activated protein kinase phosphatase 1 (DUSP1) accelerates progressive hearing loss

2018 ◽  
Author(s):  
Adelaida M Celaya ◽  
Isabel Sánchez-Pérez ◽  
Jose M Bermúdez-Muñoz ◽  
Lourdes Rodríguez-de la Rosa ◽  
Laura Pintado-Berninches ◽  
...  
eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Adelaida M Celaya ◽  
Isabel Sánchez-Pérez ◽  
Jose M Bermúdez-Muñoz ◽  
Lourdes Rodríguez-de la Rosa ◽  
Laura Pintado-Berninches ◽  
...  

Mitogen-activated protein kinases (MAPK) such as p38 and the c-Jun N-terminal kinases (JNKs) are activated during the cellular response to stress signals. Their activity is regulated by the MAPK-phosphatase 1 (DUSP1), a key component of the anti-inflammatory response. Stress kinases are well-described elements of the response to otic injury and the otoprotective potential of JNK inhibitors is being tested in clinical trials. By contrast, there are no studies exploring the role of DUSP1 in hearing and hearing loss. Here we show that Dusp1 expression is age-regulated in the mouse cochlea. Dusp1 gene knock-out caused premature progressive hearing loss, as confirmed by auditory evoked responses in Dusp1–/– mice. Hearing loss correlated with cell death in hair cells, degeneration of spiral neurons and increased macrophage infiltration. Dusp1–/– mouse cochleae showed imbalanced redox status and dysregulated expression of cytokines. These data suggest that DUSP1 is essential for cochlear homeostasis in the response to stress during ageing.


2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Yao Liu ◽  
Mei Wei ◽  
Xiang Mao ◽  
Taisheng Chen ◽  
Peng Lin ◽  
...  

The loss of auditory sensory hair cells (HCs) is the most common cause of sensorineural hearing loss (SNHL). As the main sound transmission structure in the cochlea, it is necessary to maintain the normal shape and survival of HCs. In this review, we described and summarized the signaling pathways that regulate the development and survival of auditory HCs in SNHL. The role of the mitogen-activated protein kinase (MAPK), phosphoinositide-3 kinase/protein kinase B (PI3K/Akt), Notch/Wnt/Atoh1, calcium channels, and oxidative stress/reactive oxygen species (ROS) signaling pathways are the most relevant. The molecular interactions of these signaling pathways play an important role in the survival of HCs, which may provide a theoretical basis and possible therapeutic interventions for the treatment of hearing loss.


1998 ◽  
Vol 3 (1) ◽  
pp. 23-27 ◽  
Author(s):  
Kathryn Z Guyton ◽  
Myriani Gorospe ◽  
Xiantao Wang ◽  
Yolanda D Mock ◽  
Gertrude C Kokkonen ◽  
...  

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