NEUTRAL ENDOPEPTIDASE-24.11 (NEP) ACTIVITY IN HUMAN FIBROBLASTS DURING DEVELOPMENT AND AGING

Neutral endopeptidase-24.11 (NEP, EC 3.4.24.11) is a cell surface Zn m etallopeptidase that hydrolyzes bioactive regulatory peptides. Using a spectrofluorimetric procedure, we assessed NEP activity in plasma mem branes of normal human skin and lung fibroblasts. We found a considera ble increase in NEP activity during fetal-to-adult transition. Adult s kin fibroblasts from an old donor exhibited significantly higher level s 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, adrenocort icotropin hormone (ACTH (1-24)), a regulatory peptide that can be clea ved by NEP, provoked an increase in enzymic activity in fetal and youn g adult donor fibroblasts and a decrease in this activity in fibroblas ts from adult and old donors. This finding Suggests that ageing may af fect NEP activity. (C) 1998 Elsevier Science Ireland Ltd. All rights r eserved.