BUSCADOR RECOLECTA

Digital.CSIC. Repositorio Institucional del CSIC

oai:digital.csic.es:10261/190365

Resumen del trabajo presentado al 42nd Congress of the Spanish Society of Biochemistry and Molecular Biology (SEBBM), celebrado en Madrid del 16 al 19 de julio de 2019., Sphingolipids are bioactive lipids whose role has progressed from being a mere component of cell membranes to be active participants in every cell biological process. Ceramide is the central backbone precursor of all complex bioactive sphingolipids. A myriad of functions have been described for ceramide: cell death, cell differentiation, cell proliferation, senescence, autophagy, cell cycle arrest and so on. We have addressed the study of the role that ceramide plays in the early development of inner ear in cultures of otic vesicles (OV), the primordium of this organ. This ex vivo culture mimics the in vivo development, maintaining the spatiotemporal pattern of morphogenesis. We had previously shown that a synthetic short-chain ceramide analogue was a potent inductor of apoptosis in OV cultures. The action of ceramide is finished by its phosphorylation to ceramide-1-phosphate (C1P), a reaction catalysed by ceramide kinase (CERK). C1P has been reported to be cytoprotector in OV cultures. In the chicken embryo, the insulin-like growth factor -1 (IGF-1) is required for the survival and differentiation of epithelial auditory precursors. In this work we have studied whether the pro-survival role of IGF- 1 are due to the generation of C1P. To tackle the study we have used a specific inhibitor of CERK (NVP-231). Our results show that CERK is expressed during the early inner ear development in chicken. The inhibition of CERK decreased the OV size, reduced proliferation and increased cell cycle arrest followed by cell death. The inhibition of CERK also altered the neurogenesis in the acoustic vestibular ganglion (AVG). Taken together, these results would confirm the involvement of C1P in the morphogenesis and maintenance of the OV and AVG. The exogenous IGF-1 treatment counteracted partially the effect of the inhibitor, suggesting its protective role through CERK stimulation and C1P production., This work was supported by Spanish Ministerio de Economía, Industria y Competitividad (SAF2017-86107-RFEDER) to MM and IVN., Peer reviewed