PMID- 18355445
OWN - NLM
STAT- MEDLINE
DCOM- 20080512
LR  - 20191210
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 370
IP  - 1
DP  - 2008 May 23
TI  - Ectodomain shedding of TNF-alpha is enhanced by nardilysin via activation of ADAM 
      proteases.
PG  - 154-8
LID - 10.1016/j.bbrc.2008.03.050 [doi]
AB  - Tumor necrosis factor-alpha (TNF-alpha) is released from cells by proteolytic 
      cleavage of a membrane-anchored precursor. The TNF-alpha-converting enzyme 
      (TACE/ADAM17) is the major sheddase for ectodomain shedding of TNF-alpha. 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-alpha shedding. In a cell-based shedding assay, expression of NRDc 
      synergistically enhanced TACE-induced TNF-alpha shedding. A peptide cleavage 
      assay in vitro showed that recombinant NRDc enhances the cleavage of TNF-alpha 
      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-alpha released. Co-expression of NRDc with ADAM10 
      promoted the release compared with the sole expression of ADAM10. These results 
      suggested that NRDc enhances TNF-alpha shedding through activation of not only 
      TACE but ADAM10. Our results indicate the involvement of NRDc in ectodomain 
      shedding of TNF-alpha, which may be a novel target for anti-inflammatory 
      therapies.
FAU - Hiraoka, Yoshinori
AU  - Hiraoka Y
AD  - Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto 
      University, 54 Shogoin-Kawahara-Cho, Sakyo-Ku, Kyoto 606-8507, Japan.
FAU - Yoshida, Kazuhiro
AU  - Yoshida K
FAU - Ohno, Mikiko
AU  - Ohno M
FAU - Matsuoka, Tatsuhiko
AU  - Matsuoka T
FAU - Kita, Toru
AU  - Kita T
FAU - Nishi, Eiichiro
AU  - Nishi E
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080318
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Membrane Proteins)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 451W47IQ8X (Sodium Chloride)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - EC 3.4.- (Amyloid Precursor Protein Secretases)
RN  - EC 3.4.24.- (ADAM Proteins)
RN  - EC 3.4.24.- (Metalloendopeptidases)
RN  - EC 3.4.24.61 (nardilysin)
RN  - EC 3.4.24.81 (ADAM10 Protein)
RN  - EC 3.4.24.81 (ADAM10 protein, human)
RN  - EC 3.4.24.86 (ADAM17 Protein)
RN  - EC 3.4.24.86 (ADAM17 protein, human)
SB  - IM
MH  - ADAM Proteins/antagonists & inhibitors/chemistry/*metabolism
MH  - ADAM10 Protein
MH  - ADAM17 Protein
MH  - Amyloid Precursor Protein Secretases/*metabolism
MH  - Animals
MH  - COS Cells
MH  - Catalysis
MH  - Chlorocebus aethiops
MH  - Enzyme Activation
MH  - Humans
MH  - Membrane Proteins/*metabolism
MH  - Metalloendopeptidases/chemistry/genetics/*metabolism
MH  - Protein Kinase C/metabolism
MH  - Protein Structure, Tertiary
MH  - Recombinant Proteins/chemistry/genetics/metabolism
MH  - Sodium Chloride/antagonists & inhibitors/pharmacology
MH  - Tumor Necrosis Factor-alpha/chemistry/*metabolism
EDAT- 2008/03/22 09:00
MHDA- 2008/05/13 09:00
CRDT- 2008/03/22 09:00
PHST- 2008/03/04 00:00 [received]
PHST- 2008/03/12 00:00 [accepted]
PHST- 2008/03/22 09:00 [pubmed]
PHST- 2008/05/13 09:00 [medline]
PHST- 2008/03/22 09:00 [entrez]
AID - S0006-291X(08)00518-4 [pii]
AID - 10.1016/j.bbrc.2008.03.050 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2008 May 23;370(1):154-8. doi: 
      10.1016/j.bbrc.2008.03.050. Epub 2008 Mar 18.