Linked Life Data

20806899

Source:http://linkedlifedata.com/resource/pubmed/id/20806899

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
39
pubmed:dateCreated
2010-12-14
pubmed:abstractText
Meprin ? and ?, zinc metalloproteinases, play significant roles in inflammation, including inflammatory bowel disease (IBD), possibly by activating cytokines, like interleukin 1?, interleukin 18, or tumor growth factor ?. Although a number of potential activators for meprins are known, no endogenous inhibitors have been identified. In this work, we analyzed the inhibitory potential of human plasma and identified bovine fetuin-A as an endogenous meprin inhibitor with a K(i) (inhibition constant) of 4.2 × 10(-5) M for meprin ? and a K(i) of 1.1 × 10(-6) M meprin ?. This correlated with data obtained for a fetuin-A homologue from carp (nephrosin inhibitor) that revealed a potent meprin ? and ? inhibition (residual activities of 27 and 22%, respectively) at a carp fetuin concentration of 1.5 × 10(-6) M. Human fetuin-A is a negative acute phase protein involved in inflammatory diseases, thus being a potential physiological regulator of meprin activity. We report kinetic studies of fetuin-A with the proteolytic enzymes astacin, LAST, LAST_MAM, trypsin, and chymotrypsin, indeed demonstrating that fetuin-A is a broad-range protease inhibitor. Fetuin-A inhibition of meprin ? activity was 40 times weaker than that of meprin ? activity. Therefore, we tested cystatin C, a protein structurally closely related to fetuin-A. Indeed, cystatin C was an inhibitor for human meprin ? (K(i) = 8.5 × 10(-6) M) but, interestingly, not for meprin ?. Thus, the identification of fetuin-A and cystatin C as endogenous proteolytic regulators of meprin activity broadens our understanding of the proteolytic network in plasma.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1520-4995
pubmed:author
pubmed:issnType
Electronic
pubmed:day
5
pubmed:volume
49
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
8599-607
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Fetuin-A and cystatin C are endogenous inhibitors of human meprin metalloproteases.
pubmed:affiliation
Institute of Zoology, Cell and Matrix Biology, Johannes Gutenberg-University, Johannes-von-Mu?ller-Weg 6, 55128 Mainz, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't