@article {AnttonenENEURO.0047-16.2016, author = {Tommi Anttonen and Anni Herranen and Jussi Virkkala and Anna Kirjavainen and Pinja Elomaa and Maarja Laos and Xingqun Liang and Jukka Ylikoski and Axel Behrens and Ulla Pirvola}, title = {c-Jun N-Terminal Phosphorylation: Biomarker for Cellular Stress Rather than Cell Death in the Injured Cochlea}, volume = {3}, number = {2}, elocation-id = {ENEURO.0047-16.2016}, year = {2016}, doi = {10.1523/ENEURO.0047-16.2016}, publisher = {Society for Neuroscience}, abstract = {Prevention of auditory hair cell death offers therapeutic potential to rescue hearing. Pharmacological blockade of JNK/c-Jun signaling attenuates injury-induced hair cell loss, but with unsolved mechanisms. We have characterized the c-Jun stress response in the mouse cochlea challenged with acoustic overstimulation and ototoxins, by studying the dynamics of c-Jun N-terminal phosphorylation. It occurred acutely in glial-like supporting cells, inner hair cells, and the cells of the cochlear ion trafficking route, and was rapidly downregulated after exposures. Notably, death-prone outer hair cells lacked c-Jun phosphorylation. As phosphorylation was triggered also by nontraumatic noise levels and none of the cells showing this activation were lost, c-Jun phosphorylation is a biomarker for cochlear stress rather than an indicator of a death-prone fate of hair cells. Preconditioning with a mild noise exposure before a stronger traumatizing noise exposure attenuated the cochlear c-Jun stress response, suggesting that the known protective effect of sound preconditioning on hearing is linked to suppression of c-Jun activation. Finally, mice with mutations in the c-Jun N-terminal phosphoacceptor sites showed partial, but significant, hair cell protection. These data identify the c-Jun stress response as a paracrine mechanism that mediates outer hair cell death.}, URL = {https://www.eneuro.org/content/3/2/ENEURO.0047-16.2016}, eprint = {https://www.eneuro.org/content/3/2/ENEURO.0047-16.2016.full.pdf}, journal = {eNeuro} }