Linked Life Data

17363457

Source:http://linkedlifedata.com/resource/pubmed/id/17363457

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2007-5-17
pubmed:abstractText
The skin including the microvascular endothelium is an established peripheral source and target of the immunomodulatory proopiomelanocortin (POMC) peptides ACTH and alpha-MSH. Whereas intracellular POMC peptide generation is well characterized, less is known on their extracellular processing in peripheral tissues by the neuropeptide-specific zinc metalloproteases neprilysin (NEP) and angiotensin-converting enzyme (ACE). This may locally control POMC peptide bioavailability and activation of ACTH/alpha-MSH-specific melanocortin receptors (MCs). In a cell-free system, endothelial cell (EC) membranes prepared from ACE(high)/NEP(low)-expressing primary human dermal microvascular ECs and the ACE(low)/NEP(high) expressing EC line HMEC-1 degraded ACTH(1-39) over time, resulting in temporary increased alpha-MSH immunoreactivity. Matrix-assisted laser desorption/ionization time-of-flight mass spectroscopy peptide mapping and electrospray ionization-mass spectroscopy sequencing identified several stable fragments generated from ACTH(1-39), ACTH(1-24), and alpha-MSH by EC membranes or recombinant NEP and ACE. Whereas some fragments could be assigned to a cell-specific NEP or ACE activity, other degradation products require additional enzyme activity. Pharmacological NEP inhibition enhanced the ACTH and alpha-MSH-mediated activation of EC ectopically expressing MC(1). Likewise, selected peptides such as alpha-MSH(2-12) generated from ACTH(1-39) and alpha-MSH by recombinant NEP displayed equipotent MC(1)-activating properties in vitro and antiinflammatory activity in murine allergic contact dermatitis in vivo as compared with the parental peptides. Thus, NEP and ACE significantly contribute to the EC processing of stress hormones (ACTH) and antiinflammatory peptides (alpha-MSH), which modulates MC(1) activation but does not completely inactivate the peptide ligand. Because NEP and ACE are regulated by inflammatory mediators and UV light, this may be important for ACTH/MSH-modulated skin inflammation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0013-7227
pubmed:author
pubmed:issnType
Print
pubmed:volume
148
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2793-805
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:17363457-Adrenocorticotropic Hormone, pubmed-meshheading:17363457-Amino Acid Sequence, pubmed-meshheading:17363457-Animals, pubmed-meshheading:17363457-Cell Membrane, pubmed-meshheading:17363457-Cells, Cultured, pubmed-meshheading:17363457-Endothelial Cells, pubmed-meshheading:17363457-Female, pubmed-meshheading:17363457-Humans, pubmed-meshheading:17363457-Male, pubmed-meshheading:17363457-Mice, pubmed-meshheading:17363457-Mice, Inbred C57BL, pubmed-meshheading:17363457-Molecular Sequence Data, pubmed-meshheading:17363457-Neprilysin, pubmed-meshheading:17363457-Peptidyl-Dipeptidase A, pubmed-meshheading:17363457-Pro-Opiomelanocortin, pubmed-meshheading:17363457-Protein Processing, Post-Translational, pubmed-meshheading:17363457-Recombinant Proteins, pubmed-meshheading:17363457-Skin, pubmed-meshheading:17363457-Stress, Physiological, pubmed-meshheading:17363457-alpha-MSH
pubmed:year
2007
pubmed:articleTitle
Terminating the stress: peripheral peptidolysis of proopiomelanocortin-derived regulatory hormones by the dermal microvascular endothelial cell extracellular peptidases neprilysin and angiotensin-converting enzyme.
pubmed:affiliation
Ludwig Boltzmann Institute for Cell Biology and Immunobiology of the Skin, Department of Dermatology, University of Münster, Von-Esmarch-Strasse 58, 48149 Münster, Germany. thoscho@uni-muenster.de
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't