ADAMs, a disintegrin and metalloproteinases, mediate shedding of oxytocinase
N Ito, S Nomura, A Iwase, T Ito, F Kikkawa… - Biochemical and …, 2004 - Elsevier
N Ito, S Nomura, A Iwase, T Ito, F Kikkawa, M Tsujimoto, S Ishiura, S Mizutani
Biochemical and biophysical research communications, 2004•ElsevierPlacental leucine aminopeptidase (P-LAP), a type-II transmembrane protease responsible
for oxytocin degradation during pregnancy, is converted to a soluble form through proteolytic
cleavage. The goal of this study was to determine the nature of the P-LAP secretase activity.
The hydroxamic acid-based metalloprotease inhibitors GM6001 and ONO-4817 as well as
the TNF-α protease inhibitor-2 (TAPI-2) reduced P-LAP release, while tissue inhibitors of
metalloproteinase (TIMP)-1 and TIMP-2, which are matrix metalloproteinase inhibitors, had …
for oxytocin degradation during pregnancy, is converted to a soluble form through proteolytic
cleavage. The goal of this study was to determine the nature of the P-LAP secretase activity.
The hydroxamic acid-based metalloprotease inhibitors GM6001 and ONO-4817 as well as
the TNF-α protease inhibitor-2 (TAPI-2) reduced P-LAP release, while tissue inhibitors of
metalloproteinase (TIMP)-1 and TIMP-2, which are matrix metalloproteinase inhibitors, had …
Placental leucine aminopeptidase (P-LAP), a type-II transmembrane protease responsible for oxytocin degradation during pregnancy, is converted to a soluble form through proteolytic cleavage. The goal of this study was to determine the nature of the P-LAP secretase activity. The hydroxamic acid-based metalloprotease inhibitors GM6001 and ONO-4817 as well as the TNF-α protease inhibitor-2 (TAPI-2) reduced P-LAP release, while tissue inhibitors of metalloproteinase (TIMP)-1 and TIMP-2, which are matrix metalloproteinase inhibitors, had no effect on P-LAP release in Chinese hamster ovary (CHO) cells stably overexpressing P-LAP, thus indicating possible involvement of ADAM (a disintegrin and metalloproteinase) members in P-LAP shedding. Furthermore, overexpression of ADAM9 and ADAM12 increased P-LAP release in P-LAP-CHO transfectants. Immunohistochemical analysis in human placenta demonstrated strong expression of ADAM12 in syncytiotrophoblasts, while little expression of ADAM9 was detected throughout the placenta. Our results suggest ADAM members, at least including ADAM12, are involved in P-LAP shedding in human placenta.
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