Premium
Alternate trafficking of cathepsin L in dermal fibroblasts induced by UVA radiation
Author(s) -
Klose Anke,
WilbrandHennes Astrid,
Brinckmann Jürgen,
Hunzelmann Nicolas
Publication year - 2010
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/j.1600-0625.2009.01014.x
Subject(s) - cathepsin , extracellular , cathepsin s , cathepsin l , cathepsin d , chemistry , intracellular , cathepsin a , extracellular matrix , cathepsin b , microbiology and biotechnology , cathepsin l1 , cathepsin o , biochemistry , biology , enzyme
Please cite this paper as : Alternate trafficking of cathepsin L in dermal fibroblasts induced by UVA radiation. Experimental Dermatology 2010; 19 : e117–e123. Abstract: UVA radiation is increasingly used to treat fibrotic skin disorders. However, the mechanisms underlying the therapeutic effects of UVA for these disorders are only partially understood. Cathepsin L is a lysosomal cysteine protease, which has been shown to degrade various matrix proteins thus contributing to extracellular remodeling. Therefore, we investigated whether UVA irradiation regulates the expression and release of cathepsin L in human dermal fibroblasts. No alterations were found after single irradiation; however, a significantly increased extracellular release of cathepsin L was observed after repeated irradiation up to four times. The transcript levels of cathepsin L were elevated after repetitive irradiation, leading to increased amounts of total cathepsin L protein. Furthermore, higher amounts of extracellular cathepsin L were associated with a significant reduction of intracellular processed cathepsin L and an accumulation of unprocessed procathepsin L. The use of specific inhibitors elucidated mannose phosphate‐independent sorting pathways of cathepsin L leading to enhanced secretion and reduced intracellular processing. This is the first study which demonstrates that alternate trafficking mechanisms mediate the extracellular release of a cysteine protease induced by repetitive UVA irradiation.