Ectodomain shedding of cystinyl aminopeptidase from human placental membranes.
Cystinyl aminopeptidase (CAP; EC 3.4.11.3) is an integral protein of the placental membrane that is also found in a soluble form in maternal serum during pregnancy. CAP was found to be shed from human placental membranes in a temperature- and time-dependent process. The released form of CAP was hydrophilic as assessed by phase separation in Triton X-114 and high-speed centrifugation. This ectodomain shedding of CAP was inhibited by the hydroxamic acid-based compounds marimastat and BB3103. The inhibition profile for the shedding of CAP was distinct to that for the release of angiotensin converting enzyme, implicating the involvement of distinct zinc metallosecretases in the shedding of these two proteins. These results have implications for our understanding of the mechanism underlying the reduction in serum levels of CAP observed in certain pregnancy-related disorders, such as pre-eclampsia.
Ofner
L D
LD
Proteolysis Research Group, School of Biochemistry and Molecular Biology, University of Leeds, Leeds, LS2 9JT, UK.
Hooper
N M
NM
D000328:Adult; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; D020134:Catalytic Domain; D010122:Cystinyl Aminopeptidase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010450:Endopeptidases / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D007425:Intracellular Membranes / Q000201:enzymology*; D010920:Placenta / Q000201:enzymology*; D011247:Pregnancy
C108282:BB 3103; D004791:Enzyme Inhibitors; D006877:Hydroxamic Acids; C100342:marimastat; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; D010122:Cystinyl Aminopeptidase; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human