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Deficit of mitogen-activated protein kinase phosphatase 1 (DUSP1) accelerates progressive hearing loss.

08:00 EDT 2nd April 2019 | BioPortfolio

Summary of "Deficit of mitogen-activated protein kinase phosphatase 1 (DUSP1) accelerates progressive hearing loss."

Mitogen-activated protein kinases (MAPK) p38 and 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. In contrast, there are no studies exploring the role of DUSP1 in hearing and hearing loss. Here we show that expression is age-regulated in the mouse cochlea. gene knock-out caused premature progressive hearing loss, as confirmed by auditory evoked responses in mice. Hearing loss correlated with cell death in hair cells, degeneration of spiral neurons and increased macrophage infiltration. mouse cochleae showed imbalanced redox status and deregulated expression of cytokines. These data suggest that DUSP1 is essential for cochlear homeostasis in the response to stress during ageing.

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This article was published in the following journal.

Name: eLife
ISSN: 2050-084X
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Medical and Biotech [MESH] Definitions

A mitogen-activated protein kinase kinase with specificity for a subset of P38 MITOGEN-ACTIVATED PROTEIN KINASES that includes MITOGEN-ACTIVATED PROTEIN KINASE 12; MITOGEN-ACTIVATED PROTEIN KINASE 13; and MITOGEN-ACTIVATED PROTEIN KINASE 14.

A member of the ternary complex family of ets-related transcription factors that is regulated by MITOGEN-ACTIVATED PROTEIN KINASES including JNK MITOGEN-ACTIVATED PROTEIN KINASES; MITOGEN-ACTIVATED PROTEIN KINASE 1; MITOGEN-ACTIVATED PROTEIN KINASE 3; and P38 MITOGEN-ACTIVATED PROTEIN KINASES.

A mitogen-activated protein kinase kinase with specificity for JNK MITOGEN-ACTIVATED PROTEIN KINASES; P38 MITOGEN-ACTIVATED PROTEIN KINASES and the RETINOID X RECEPTORS. It takes part in a SIGNAL TRANSDUCTION pathway that is activated in response to cellular stress.

A superfamily of PROTEIN-SERINE-THREONINE KINASES that are activated by diverse stimuli via protein kinase cascades. They are the final components of the cascades, activated by phosphorylation by MITOGEN-ACTIVATED PROTEIN KINASE KINASES, which in turn are activated by mitogen-activated protein kinase kinase kinases (MAP KINASE KINASE KINASES).

Mitogen-activated protein kinase kinase kinases (MAPKKKs) are serine-threonine protein kinases that initiate protein kinase signaling cascades. They phosphorylate MITOGEN-ACTIVATED PROTEIN KINASE KINASES; (MAPKKs) which in turn phosphorylate MITOGEN-ACTIVATED PROTEIN KINASES; (MAPKs).

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