Cohen Marie, Wuillemin Christine, Chai Siew Yeen, Bischof Paul
Department of Obstetrics and Gynaecology, Maternity, Laboratory of Hormonology, University of Geneva, Boulevard de la Cluse, Geneva 14, Switzerland.
J Pept Sci. 2008 Jul;14(7):883-7. doi: 10.1002/psc.1018.
Insulin-regulated aminopeptidase (IRAP) activity increases during placentation and in the invasive tumor cell of trophoblast suggesting a role for this peptidase in the invasiveness of normal and malignant trophoblast. To investigate this hypothesis, we studied the effects of substrate (OT) and inhibitors (angiotensin peptides and LVV-H7) of IRAP on the first trimester trophoblast proliferation and invasion. Addition of these peptides in the culture medium of trophoblastic cells significantly decreased metalloproteinase-9 activity and cellular invasiveness while no effect was observed on cell proliferation. The peptide IRAP inhibitors could exert their effect on cytotrophoblastic cell invasiveness by inhibition of its enzymatic activity, and thus increasing half life of the known placental peptide substrate of IRAP, OT.
胰岛素调节氨肽酶（IRAP）的活性在胎盘形成过程中以及滋养层侵袭性肿瘤细胞中会增加，这表明该肽酶在正常和恶性滋养层的侵袭性中发挥作用。为了研究这一假设，我们研究了IRAP的底物（催产素）和抑制剂（血管紧张素肽和LVV-H7）对孕早期滋养层细胞增殖和侵袭的影响。在滋养层细胞培养基中添加这些肽显著降低了金属蛋白酶-9的活性和细胞侵袭性，而对细胞增殖未观察到影响。肽类IRAP抑制剂可通过抑制其酶活性对细胞滋养层细胞侵袭性发挥作用，从而延长IRAP已知的胎盘肽底物催产素的半衰期。
