Skin barrier lipid enzyme activity in Netherton patients is associated with protease activity and ceramide abnormalities [Research Articles]

We examined two key enzymes involved in epidermal ceramide biosynthesis, β-glucocerebrosidase (GBA) and acid-sphingomyelinase (ASM). We compared in situ expression levels and activities of GBA and ASM between NTS patients and controls and correlated the expression and activities with i) SC ceramide profiles, ii) in situ serine protease activity, and iii) clinical presentation of patients. Using activity-based probe labeling, we visualized and localized active epidermal GBA, and a newly developed in situ zymography method enabled us to visualize and localize active ASM. Reduction in active GBA in NTS patients coincided with increased ASM activity, particularly in areas with increased serine protease activity. NTS patients with scaly erythroderma exhibited more pronounced anomalies in GBA and ASM activities than patients with ichthyosis linearis circumflexa. They also displayed a stronger increase in SC ceramides processed via ASM. We conclude that changes in the localization of active GBA and ASM correlate with i) altered SC ceramide composition in NTS patients, ii) local serine protease activity, and iii) the clinical manifestation of NTS.

Source: The Journal of Lipid Research - May 31, 2020 Category: Lipidology Authors: van Smeden, J., Al-Khakany, H., Wang, Y., Visscher, D., Stephens, N., Absalah, S., Overkleeft, H. S., Aerts, J. M. F. G., Hovnanian, A., Bouwstra, J. A. Tags: Research Articles Source Type: research