Acid-stable serine proteinase inhibitors in the urine of Alzheimer disease subjects.

A comparative study of the levels of acid-stable proteinase inhibitors (kallikrein and trypsin inhibitors) in the urine of healthy and Alzheimer subjects, of both sexes, has been performed. A preliminary characterization of the purified inhibitors indicates that the urinary antitryptic activity is accounted for by the presence of the well known Urinary Trypsin Inhibitor (UTI) while an apparently new molecule appears to be responsible for the antikallikrein activity. The urinary levels of kallikrein inhibitors are very similar in healthy and sick subjects while the levels of trypsin inhibitors appear significatively increased in Alzheimer subjects of both sexes. The data presented here support the hypothesis that unpaired proteolytic processes could be involved in the pathogenesis of Alzheimer's disease and suggest that the levels of urinary acid-stable inhibitors may prove to be useful markers of the disease.

[1]  K. Sugaya,et al.  Tissue kallikrein in rat and mouse neurons. , 1994, Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas.

[2]  F. Ascoli,et al.  High-performance liquid chromatographic separation of aprotinin-like inhibitors and their determination in very small amounts. , 1993, Journal of chromatography.

[3]  E. Koo,et al.  A calcium-stimulated serine protease from monkey brain degrades the β-amyloid precursor protein , 1992, Brain Research.

[4]  Takesada Mori,et al.  Expression of pancreatic secretory trypsin inhibitor gene in human colorectal tumor , 1990 .

[5]  H. Potter,et al.  Alzheimer's Disease: Recent Advances in Understanding the Brain Amyloid Deposits , 1989, Bio/Technology.

[6]  D. Selkoe,et al.  Immunochemical identification of the serine protease inhibitor α 1-antichymotrypsin in the brain amyloid deposits of Alzheimer's disease , 1988, Cell.

[7]  S. Shiojiri,et al.  Novel precursor of Alzheimer's disease amyloid protein shows protease inhibitory activity , 1988, Nature.

[8]  B. Greenberg,et al.  A new A4 amyloid mRNA contains a domain homologous to serine proteinase inhibitors , 1988, Nature.

[9]  P. Patterson,et al.  Characterization of an inhibitor of neuronal plasminogen activator released by heart cells , 1987, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[10]  R. Pittman Release of plasminogen activator and a calcium-dependent metalloprotease from cultured sympathetic and sensory neurons. , 1985, Developmental biology.

[11]  C. Masters,et al.  Amyloid plaque core protein in Alzheimer disease and Down syndrome. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[12]  M. Folstein,et al.  Clinical diagnosis of Alzheimer's disease , 1984, Neurology.

[13]  H. Ezaki,et al.  Isolation of urinary trypsin inhibitor-like inhibitor from human lung cancer tissue. , 1984, Cancer research.

[14]  N. Seeds,et al.  Peripheral neurons and Schwann cells secrete plasminogen activator , 1984, The Journal of cell biology.

[15]  G. Kōsaki,et al.  Elevation of serum immunoreactive pancreatic secretory trypsin inhibitor contents in various malignant diseases. , 1983, Research communications in chemical pathology and pharmacology.

[16]  U. Stenman,et al.  Purification and characterization of a tumor-associated trypsin inhibitor from the urine of a patient with ovarian cancer. , 1982, The Journal of biological chemistry.

[17]  D. Rudman,et al.  Relation of the Urinary Cancer-Related Glycoprotein EDC1 to Plasma Inter-α -Trypsin Inhibitor , 1978, The Journal of Immunology.

[18]  U. K. Laemmli,et al.  Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4 , 1970, Nature.

[19]  N. Shulman A proteolytic inhibitor with anticoagulant activity separated from human urine and plasma. , 1955, The Journal of biological chemistry.

[20]  D. Selkoe,et al.  α-1-Antichymotrypsin, a Serine Protease Inhibitor, is a Component of the Amyloid Deposits in Alzheimer’s Disease , 1988 .

[21]  L. Villa-komaroff,et al.  Protease inhibitor domain encoded by an amyloid protein precursor mRNA associated with Alzheimerʼs disease , 1988 .

[22]  N. Matsuura,et al.  Expression of pancreatic secretory trypsin inhibitor in various cancer cells. , 1987, Research communications in chemical pathology and pharmacology.

[23]  G. Citro,et al.  Characterization of three new Kunitz-type inhibitors from bovine spleen: preparation of specific antibodies. , 1985, Preparative biochemistry.

[24]  G. Citro,et al.  Immunochemical studies on the Kunitz type inhibitors from bovine spleen. , 1984, Preparative biochemistry.

[25]  H. Fritz,et al.  Biochemistry and applications of aprotinin, the kallikrein inhibitor from bovine organs. , 1983, Arzneimittel-Forschung.

[26]  G. Salvesen,et al.  Human plasma proteinase inhibitors. , 1983, Annual review of biochemistry.

[27]  I. Kato,et al.  Protein inhibitors of proteinases. , 1980, Annual review of biochemistry.