Neutral endopeptidase-24.11 (NEP) activity in human fibroblasts during development and ageing.
Neutral endopeptidase-24.11 (NEP, EC 3.4.24.11) is a cell surface Zn metallopeptidase that hydrolyzes bioactive regulatory peptides. Using a spectrofluorimetric procedure, we assessed NEP activity in plasma membranes of normal human skin and lung fibroblasts. We found a considerable increase in NEP activity during fetal-to-adult transition. Adult skin fibroblasts from an old donor exhibited significantly higher levels of NEP activity than cells from young donors. Interestingly, however, the NEP activity of fibroblasts from a centenarian donor was similar to that of cells from young donors. Increased levels of NEP activity were also found in in vitro aged lung fibroblasts. Finally, adrenocorticotropin hormone (ACTH (1-24)), a regulatory peptide that can be cleaved by NEP, provoked an increase in enzymic activity in fetal and young adult donor fibroblasts and a decrease in this activity in fibroblasts from adult and old donors. This finding suggests that ageing may affect NEP activity.
Kletsas
D
D
Institute of Biology, National Center for Scientific Research Demokritos, Athens, Greece.
Caselgrandi
E
E
Barbieri
D
D
Stathakos
D
D
Franceschi
C
C
Ottaviani
E
E
D000328:Adult; D000368:Aged; D002455:Cell Division; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects / Q000502:physiology; D002648:Child; D003366:Cosyntropin / Q000494:pharmacology; D005333:Fetus; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology*; D006020:Glycopeptides / Q000494:pharmacology; D006801:Humans; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D015260:Neprilysin / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism*; D011480:Protease Inhibitors / Q000494:pharmacology; D012867:Skin / Q000166:cytology / Q000187:drug effects / Q000201:enzymology
D006020:Glycopeptides; D011480:Protease Inhibitors; D003366:Cosyntropin; D015260:Neprilysin; C008890:phosphoramidon