204 Is the proteasome activity involved in filaggrin breakdown?

Epidermal hydration is maintained mainly by the retention of water in stratum corneum through natural moisturizing factor (NMF). NMF a complex mixture components, including pyrrolidone carboxylic acid (PCA) and urocanic (UCA), two amino derivatives. In corneum, breakdown filaggrin (FLG) main source PCA UCA. The proteases involved this degradation are still incompletely known. keratosis linearis with ichthyosis congenital sclerosing keratoderma (KLICK) syndrome, defect proteasome maturation protein POMP causes an altered epidermal distribution multi-protein complex, associated enlarge rounded shaped keratohyalin granules disturbed detection FLG. We hypothesized that FLG degradation. 3D reconstructed human epidermis, produced at air-liquid interface low relative humidity condition (30-50%), were treated for 24 hours various concentrations irreversible inhibitor clasto-lactacystin b-lactone, analyzed using histochemistry, indirect immuno-fluorescence, transmission electron microscopy, western blotting UHPLC linked to mass spectrometry. After b-lactone treatment, as expected, significant accumulation ubiquitinated proteins was observed, without any major cytotoxic effects compared controls. morphological integrity epidermis maintain, even if many small vesicles spherical observed cytoplasm differentiated keratinocytes. treatment induced decrease immunodetection. However, amount UCA did not show drastic differences between untreated conditions. Therefore, activity seems directly but may act during keratinocyte differentiation homeostasis.