BUSCADOR RECOLECTA

Digital.CSIC. Repositorio Institucional del CSIC

oai:digital.csic.es:10261/190610

Resumen del trabajo presentado al 42st Annual Association for Research in Otolaryngology (ARO) MidWinter Meeting, celebrado en Baltimore, Maryland (USA) del 9 al 13 de febrero de 2019., P38 mitogen-activated protein (MAP) kinases p38α, β, γ and δ are codified by Mapk14, 11, 12 and 13 genes, respectively. P38 kinases are activated by phosphorylation in response to a variety of extracellular stress stimuli that transduce to the nuclei. The MAPK14 (p38a) isoform is ubiquitously expressed and is critical for mammalian embryonic development. MAPK14 participates in the cochlear response to stressors like cisplatin, UV radiation or noise exposure. MAPK14 expression and activity also increase as a consequence of Igf1 deletion in mice in association with hearing loss and cellular apoptosis. We have studied the expression pattern of the four p38 isoforms along ageing in wild type and knock out Igf1 null mice, to show that they are age- and IGF-1- regulated. To further explore the role of Mapk14 in the cochlea, we have studied the Mapk14lox/loxRERTnERT/ERT conditional knock out mouse and cell lines derived from embryonic fibroblasts. Mapk14 knock out mice auditory brainstem responses (ABR) recording showed that ABR thresholds do not vary upon Mapk14 deletion induced by tamoxifen treatment. RT-qPCR gene expression studies of the p38 isoforms indicated that other isoforms are induced and maybe taking over MAPK14 cochlear functions. P38 isoforms relative expression levels also varied in Mapk14-knock out fibroblasts, as well as the transcripts for MEF2, FoxM1 and FoxG1, which are also altered in the cochlea of Igf1-null mice. Finally, we assessed the response to noise-induced injury in Cre/loxP Mapk14 knock out mice before and after noise exposure. Interestingly, mice with total or partial deletion of Mapk14 exposed to violet noise at an intensity of 105 dB SPL during 30 minutes showed a better recovery of hearing thresholds than wild type mice. These data suggest that MAPK14 plays a central role in the progression of cochlear damage after noise exposure., Research was supported by Spanish MINECO/FEDER SAF2017-86107-R and EU FP7-PEOPLE-TARGEAR grants to IV-N. LRR and SMC hold CIBERER contracts. AGM holds a MECD FPU fellowship., Peer Reviewed