EVIDENCE AGAINST A ROLE FOR THE KUNITZ DOMAIN IN AMYLOIDOGENIC AND SECRETORY PROCESSING OF THE AMYLOID PRECURSOR PROTEIN

被引:0
|
作者
LADROR, US
KOHNKEN, RE
WANG, GT
MANELLI, AM
FRAIL, DE
KLEIN, WL
HOLZMAN, TF
KRAFFT, GA
机构
[1] ABBOTT LABS,DIV PHARMACEUT PROD,ABBOTT PK,IL 60064
[2] NORTHWESTERN UNIV,DEPT NEUROBIOL,EVANSTON,IL
关键词
BETA-AMYLOID PRECURSOR PROTEIN; KUNITZ PROTEINASE INHIBITOR; ALZHEIMERS DISEASE;
D O I
暂无
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The effect of the Kunitz proteinase inhibitor (KPI) on potential beta-amyloid precursor protein (beta PP)-processing activities from control and Alzheimer's disease (AD) brains was examined using fluorogenic substrates designed to mimic the secretory and amyloidogenic cleavages in beta PP. In addition, the level of secretion of KPI-containing beta PP751 and KPI-lacking beta PP695 from transfected cells was examined to assess the effect of the KPI on beta PP secretion. beta PP751 and beta PP695, obtained from conditioned media of transfected cells, had no effect on proteinase activities against the secretory and amyloidogenic substrates in extracts from control and AD brains. At similar concentrations beta PP751, but not beta PP695, completely inhibited the activity of trypsin against these substrates. Serine proteinase inhibitors had only modest effects on activities from brain, whereas cysteine modification completely inhibited them, indicating that these proteinase activities were not of the serine type. Thus, the results do not support a role for the KPI in the secretion of beta PP or in the amyloidogenic cleavage of beta PP. The amounts of beta PP695 and beta PP751 collected from the media of transfected cells after 48 h of growth were similar, indicating an equal rate of secretion. This result suggests that the KPI domain in beta PP751 did not inhibit the secretory cleavage in transfected cells.
引用
收藏
页码:2225 / 2230
页数:6
相关论文
共 50 条
  • [1] Amyloidogenic processing of β-amyloid precursor protein in intracellular compartments
    Vetrivel, KS
    Thinakaran, G
    [J]. NEUROLOGY, 2006, 66 : S69 - S73
  • [2] Amyloidogenic processing of amyloid precursor protein:: Evidence of a pivotal role of glutaminyl cyclase in generation of pyroglutamate-modified amyloid-β
    Cynis, Holger
    Scheel, Eike
    Saido, Takaomi C.
    Schilling, Stephan
    Demuth, Hans-Ulrich
    [J]. BIOCHEMISTRY, 2008, 47 (28) : 7405 - 7413
  • [3] PROCESSING OF THE AMYLOID PROTEIN-PRECURSOR TO POTENTIALLY AMYLOIDOGENIC DERIVATIVES
    GOLDE, TE
    ESTUS, S
    YOUNKIN, LH
    SELKOE, DJ
    YOUNKIN, SG
    [J]. SCIENCE, 1992, 255 (5045) : 728 - 730
  • [4] PROCESSING OF THE AMYLOID PROTEIN-PRECURSOR TO POTENTIALLY AMYLOIDOGENIC DERIVATIVES
    GOLDE, TE
    ESTUS, S
    YOUNKIN, LH
    SELKOE, DJ
    YOUNKIN, SG
    [J]. JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY, 1992, 51 (03): : 370 - 370
  • [5] Characterization of the role of Kunitz-type protease inhibitor domain in dimerization of amyloid precursor protein
    Byun, Jinyoung
    Vellampatti, Srivithya
    Chatterjee, Prathit
    Hwang, Sun Ha
    Kim, Byoung Choul
    Lee, Juyong
    [J]. JOURNAL OF COMPUTATIONAL CHEMISTRY, 2023, 44 (15) : 1437 - 1445
  • [6] Capsaicin promotes the amyloidogenic route of brain amyloid precursor protein processing
    Pakaski, Magdolna
    Hugyecz, Marietta
    Santha, Peter
    Jancso, Gabor
    Bjelik, Annamaria
    Domokos, Agnes
    Janka, Zoltan
    Kalman, Janos
    [J]. NEUROCHEMISTRY INTERNATIONAL, 2009, 54 (07) : 426 - 430
  • [7] A splice variant of β-secretase deficient in the amyloidogenic processing of the amyloid precursor protein
    Bodendorf, U
    Fischer, F
    Bodian, D
    Multhaup, G
    Paganetti, P
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (15) : 12019 - 12023
  • [8] Palmitoylation of Amyloid Precursor Protein Regulates Amyloidogenic Processing in Lipid Rafts
    Bhattacharyya, Raja
    Barren, Cory
    Kovacs, Dora M.
    [J]. JOURNAL OF NEUROSCIENCE, 2013, 33 (27): : 11169 - 11183
  • [9] Amyloidogenic processing of the Alzheimer β-amyloid precursor protein depends on lipid rafts
    Ehehalt, R
    Keller, P
    Haass, C
    Thiele, C
    Simons, K
    [J]. JOURNAL OF CELL BIOLOGY, 2003, 160 (01): : 113 - 123
  • [10] The alternatively spliced Kunitz protease inhibitor domain alters amyloid beta protein precursor processing and amyloid beta protein production in cultured cells
    Ho, LB
    Fukuchi, K
    Younkin, SG
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (48) : 30929 - 30934