Amyloidosis is a chronic degenerative disease that is characterized by the deposition of fibrous $ beta$-pleated amyloid proteins in various soft tissues and organs (Glenner 1980, Kisilevsky 1983 & 1987). Sporadic form of Alzheimer's disease is one of the most common forms of systemic amyloidosis, with the current prevalence of approximately 4 million cases in the United States and 6 to 8 million cases worldwide (Kisilevsky 1987, Coleman 1990). / Amyloidosis can be experimentally induced in animals. In the inflammation-associated mouse model of amyloidosis, the preamyloid phase, which usually lasts for a number of weeks, is shortened to 24 to 48 hr in the recipient mice upon the administration of amyloid enhancing factor (AEF). AEF activity is present in a much higher level in amyloidotic animals, as well as the amyloidotic tissues in humans (Werdlin and Ranlov 1966, Kisilevsky 1983, Ali-Khan et al. 1988, Alizadeh-Khiavi et al. 1988). / Using brain extracts from Alzheimer patients and liver and spleen extracts from our well-characterized alveolar hydatid cyst (AHC)-mouse model of amyloidosis (Ali-Khan et al. 1983b, Alkarmi and Ali-Khan 1984, Abankwa and Ali-Khan 1988a & 1988b, Alizadeh-Khiavi and Ali-Khan 1988, Du and Ali-Khan 1990) I have been able to purify ubiquitin (UB) and demonstrate its AEF activity in mice (Alizadeh-Khiavi and Ali-Khan 1990, Alizadeh-Khiavi et al. 1990a & 1990b). UB, a stress protein universally found in all eukaryotes, can function as a sentinel-like molecule in the degradation of short-lived or abnormal proteins (Rechsteiner 1987). At a level as low as 10 $ mu$g, the tissue derived UB shows potent AEF activity in the mouse bioassay. The fact that recombinant wild type ubiquitin (R-UB) possess AEF activity, that the AEF activity of both crude and R-UB is abolished by anti-ubiquitin antibody, and that the same antibody inhibits the in vitro amyloidogenic activity by ubiquitin-rich macrophages, further establishes the role of ubiquitin in amyloidogenesis. Using immunohistochemistry and immuno-electron microscopy I have confirmed the cell origin of AEF/ubiquitin, localized its presence in the intracellular compartments of polymorphonuclear leukocytes and macrophages, and demonstrated its binding to murine AA amyloid.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.70161 |
| Date | January 1991 |
| Creators | Alizadeh-Khiavi, Kamel |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Doctor of Philosophy (Department of Microbiology and Immunology.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001215160, proquestno: AAINN67501, Theses scanned by UMI/ProQuest. |
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