P4-153: The disruption of A-Beta peptide by transthyretin: A mechanism sensitive to Kunitz Protease Inhibitor

Radiolabeled annexin V (ANV) has been widely used for imaging cell apoptosis. Recently, a novel ANV-Kunitz-type protease inhibitor fusion protein, ANV-6L15, was found to be a promising probe for improved apoptosis detection based on its higher affinity to phosphatidylserine (PS) compared to native ANV. The present paper investigates the feasibility of apoptosis detection using radioiodinated ANV-6L15. Native ANV and ANV-6L15 were labeled with iodine-123 and iodine-125 using Iodogen method. The binding between the radioiodinated proteins and erythrocyte ghosts or chemical-induced apoptotic cells was examined. ANV-6L15 can be radioiodinated with high yield (40%−60%) and excellent radiochemical purity (>95%).123I-ANV-6L15 exhibited a higher binding ratio to erythrocyte ghosts and apoptotic cells compared to123I-ANV. The biodistribution of123I-ANV-6L15 in mice was also characterized.123I-ANV-6L15 was rapidly cleared from the blood. High uptake in the liver and the kidneys may limit the evaluation of apoptosis in abdominal regions. Our data suggest that radiolabled ANV-6L15 may be a better scintigraphic tracer than native ANV for apoptosis detection.

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Kunitz Protease Inhibitor-Containing Amyloid β Protein Precursor Immunoreactivity in Alzheimer's Disease

Journal of Neuropathology & Experimental Neurology ◽

10.1097/00005072-199201000-00009 ◽

1992 ◽

Vol 51 (1) ◽

pp. 76-83 ◽

Cited By ~ 96

Author(s):

B. T. Hyman ◽

R. E. Tanzi ◽

K. Marzloff ◽

R. Barbour ◽

D. Schenk

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Protease Inhibitor ◽

Amyloid Β ◽

Amyloid Β Protein ◽

Protein Precursor ◽

Β Protein ◽

Kunitz Protease Inhibitor

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A genetically engineered human Kunitz protease inhibitor with increased kallikrein inhibition in an ovine model of cardiopulmonary bypass

Perfusion ◽

10.1177/026765910101600305 ◽

2001 ◽

Vol 16 (3) ◽

pp. 199-206 ◽

Cited By ~ 3

Author(s):

Sunil K Ohri ◽

Rachel Parratt ◽

Tyler White ◽

Jenny Becket ◽

John J Brannan ◽

...

Keyword(s):

Cardiopulmonary Bypass ◽

Protease Inhibitor ◽

Randomized Study ◽

Genetically Engineered ◽

Wild Type ◽

Ovine Model ◽

Double Blind ◽

Perioperative Bleeding ◽

Kunitz Inhibitor ◽

Kunitz Protease Inhibitor

A recombinant human serine protease inhibitor known as Kunitz protease inhibitor (KPI) wild type has functional similarities to the bovine Kunitz inhibitor, aprotinin, and had shown a potential to reduce bleeding in an ovine model of cardiopulmonary bypass (CPB). The aim of this study was to assess KPI-185, a modification of KPI-wild type that differs from KPI-wild type in two amino acid residues and which enhances anti-kallikrein activity in a further double-blind, randomized study in an ovine model of CPB, and to compare with our previous study of KPI-wild type and aprotinin in the same ovine model. Post-operative drain losses and subjective assessment of wound ‘dryness’ showed no significant differences between KPI-185 and KPI-wild type, despite the significant enhancement of kallikrein inhibition using KPI-185 seen in serial kallikrein inhibition assays. These preliminary findings support the hypothesis that kallikrein inhibition is not the major mechanism by which Kunitz inhibitors such as aprotinin reduce perioperative bleeding.

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Identification of a filamentous form of kunitz protease inhibitor in Asteraceae

10.1101/2021.01.22.427805 ◽

2021 ◽

Author(s):

Sara Bratsch ◽

Neil Olszewski ◽

Benham Lockhart

Keyword(s):

Protease Inhibitor ◽

Protein Sequencing ◽

Major Protein ◽

Kunitz Trypsin Inhibitor ◽

Terminal Protein ◽

Filamentous Form ◽

First Report ◽

Kunitz Protease Inhibitor ◽

Sds Page ◽

Filament Protein

AbstractFilamentous structures were observed in purified extracts from chrysanthemum, gerbera, sunflower and zinnia. When purified filament proteins were subjected to SDS-PAGE, the major protein associated with filaments from all three species has an apparent molecular mass of ≈25 kDa. Protein bands from chrysanthemum, gerbera, and zinnia were subjected to N-terminal protein sequencing while proteins from sunflower were sequenced by CID MS/MS. All of the sequences shared highest similarity to the kunitz trypsin inhibitor family. The sequencing results indicated that the proteins lacked the signal sequences. We tested the gerbera filament protein for glycosylation and found that it was a glycoprotein. Together these results indicate that the filaments are composed of mature KTI protein. This is the first report of a KTI assembling into filaments and the first report of a filament forming Asteraceae enzyme.

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