کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1935869 | 1050676 | 2008 | 5 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Ectodomain shedding of TNF-α is enhanced by nardilysin via activation of ADAM proteases Ectodomain shedding of TNF-α is enhanced by nardilysin via activation of ADAM proteases](/preview/png/1935869.png)
Tumor necrosis factor-α (TNF-α) is released from cells by proteolytic cleavage of a membrane-anchored precursor. The TNF-α-converting enzyme (TACE/ADAM17) is the major sheddase for ectodomain shedding of TNF-α. At present, however, it is poorly understood how its catalytic activity is regulated. Here, we show that nardilysin (N-arginine dibasic convertase; NRDc) enhanced TNF-α shedding. In a cell-based shedding assay, expression of NRDc synergistically enhanced TACE-induced TNF-α shedding. A peptide cleavage assay in vitro showed that recombinant NRDc enhances the cleavage of TNF-α induced by TACE. Notably, co-incubation of NRDc completely reversed the inhibitory effect of a physiological concentration of salt on TACE’s activity in vitro. Overexpression of NRDc in TACE-deficient fibroblasts resulted in an increase in the amount of TNF-α released. Co-expression of NRDc with ADAM10 promoted the release compared with the sole expression of ADAM10. These results suggested that NRDc enhances TNF-α shedding through activation of not only TACE but ADAM10. Our results indicate the involvement of NRDc in ectodomain shedding of TNF-α, which may be a novel target for anti-inflammatory therapies.
Journal: Biochemical and Biophysical Research Communications - Volume 370, Issue 1, 23 May 2008, Pages 154–158