Sustained serine proteases activity by prolonged increase in pH leads to degradation of lipid processing enzymes and profound alterations of barrier function and stratum corneum integrity

JOURNAL OF INVESTIGATIVE DERMATOLOGY

卷:125

Article

Hachem, JP ; Man, MQ ; Crumrine, D ; Uchida, Y ; Brown, BE ; Rogiers, V ; Roseeuw, D ; Feingold, KR ; Elias, PM

关键词: barrier function;    cohesion;    corneodesmosomes;    integrity;    serine protease;    serine protease inhibitors;    stratum corneum;    superbase;    transepidermal water loss;   

DOI  :  10.1111/j.0022-202X.2005.23838.x

来源: Elsevier

【 摘 要 】

We showed recently that short-term increases in stratum corneum (SC) pH are accompanied by minor alterations in permeability barrier homeostasis and SC integrity/cohesion. Since prolonged SC neutralization more closely mirrors clinical situations (i.e., neonatal skin, occupational dermatitis conditions), we assessed here whether sustained elevations of SC pH by long-term application of 1,1,3,3-tetramethylguanidine superbase provoke profound alterations in SC function. Sustained SC neutralization altered not only barrier recovery kinetics but also basal permeability barrier function. These abnormalities were attributable to a decrease in beta-glucocerebrosidase (beta-GlcCer'ase) and acidic sphingomyelinase (aSMase) catalytic activity and enzyme degradation consequent to a pH-induced sustained serine protease (SP) activity. The role of SP in this process was shown by the normalization of enzyme activities/content by co-applied SP inhibitors (SPI). To address whether lipid-processing enzymes are potential substrates for the stratum corneum chymotryptic enzyme (SCCE), protein extracts from human SC were treated for 2 h at 37 degrees C with recombinant active SCCE at pH 7.2. Recombinant SCCE induced a significant decrease in the immunoblotting of both beta-GlcCer'ase or aSMase compared with control experiments performed in the absence of the active SCCE. Finally, with sustained SC neutralization, SC integrity/cohesion deteriorated, attributable to SP-mediated degradation of corneodesmosomes (CD) as well as CD constituent proteins, desmoglein 1. These abnormalities were again reversed by co-applied SPI. In conclusion, prolonged SC neutralization provokes profound abnormalities in SC function, due to pH-induced high SP activity that, in turn, degrades lipid processing enzymes and CD proteins.

【 授权许可】

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