In:
Experimental Dermatology, Wiley, Vol. 21, No. 10 ( 2012-10), p. 751-757
Abstract:
Peroxisome proliferator‐activated receptor ( PPAR ) delta agonists are known to have distinct anti‐inflammatory and antitumor effects; though, the knowledge regarding their mode of action has thus far been limited. Different cathepsins have been shown to be upregulated in a broad range of pathological events, such as rheumatoid arthritis, psoriasis, atherosclerosis and diverse tumor entities, for example melanoma. Recent work demonstrated that cathepsin B in particular is an important pro‐angiogenic protease in various pathological conditions. We therefore analysed whether cathepsins are a valid target for PPAR δ agonists. This study reveals an inhibitory effect of two commonly used PPAR δ agonists, GW 501516 and L ‐165,041, on the protein expression and enzyme activity of cathepsin B in human endothelial cells. In contrast, no inhibitory effects were observed on cathepsin L and cathepsin D protein expression after treatment with PPAR δ agonists. Furthermore, the results substantiate that PPAR δ activators mediate their inhibitory action in a PPAR δ‐dependent manner and that the underlying regulatory mechanism is not based on a transcriptional but rather on a posttranslational mode of action, via the reduction in the cathepsin B protein half‐life. Mechanisms conveying the suppressive effect by 5′‐alternative splicing, a 3′‐ UTR ‐dependent way or by mi RNA could be excluded. The data of this study explore cathepsin B as a new valid target for PPAR δ agonists in endothelial cells. The results bolster other studies demonstrating PPAR δ agonists as anti‐inflammatory and anticarcinogenic agents and thus might have the potential to help to develop new pharmaceutical drugs.
Type of Medium:
Online Resource
ISSN:
0906-6705
,
1600-0625
DOI:
10.1111/exd.2012.21.issue-10
Language:
English
Publisher:
Wiley
Publication Date:
2012
detail.hit.zdb_id:
2026228-0
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