scholarly journals Conformational stability of the RNP domain controls fibril formation of PABPN1

2015 ◽  
Vol 24 (11) ◽  
pp. 1789-1799
Author(s):  
Jens Liebold ◽  
Reno Winter ◽  
Ralph Golbik ◽  
Gerd Hause ◽  
Christoph Parthier ◽  
...  
Keyword(s):  
Conformational Stability ◽  
Fibril Formation ◽  
Rnp Domain

scholarly journals Effect of Association State and Conformational Stability on the Kinetics of Immunoglobulin Light Chain Amyloid Fibril Formation at Physiological pH

2002 ◽  
Vol 277 (15) ◽  
pp. 12657-12665 ◽  
Author(s):  
Pierre O. Souillac ◽  
Vladimir N. Uversky ◽  
Ian S. Millett ◽  
Ritu Khurana ◽  
Sebastian Doniach ◽  
...  
Keyword(s):  
Light Chain ◽  
Amyloid Fibril ◽  
Conformational Stability ◽  
Fibril Formation ◽  
Immunoglobulin Light Chain ◽  
Amyloid Fibril Formation ◽  
Kinetics Of ◽  
Association State

Immunocytochemical Localization of Amyloid Protein AA in the “Dense Fibrillar Inclusions” of the Reticuloendothelical Cells

1977 ◽  
Vol 35 ◽  
pp. 438-439
Author(s):  
T. Shirahama ◽  
M. Skinner ◽  
A.S. Cohen
Keyword(s):  
Amyloid Fibril ◽  
Close Association ◽  
Gel Filtration ◽  
Fibril Formation ◽  
Amyloid Protein ◽  
Electron Microscopic ◽  
Amyloid Deposits ◽  
Amyloid Fibril Formation ◽  
Electron Microscopic Technique ◽  
Lysosomal System

A1thought the mechanisms of amyloidogenesis have not been entirely clarified, proteolysis of the parent proteins may be one of the important steps in the amyloid fibril formation. Recently, we reported that "dense fibrillar inclusions" (DFI), which had the characteristics of lysosomes and contained organized fibrillar profiles as well, were observed in the reticuloendothelial cells in close association with the foci of new amyloid deposits. We considered the findings as evidence for the involvement of lysosomal system in amyloid fibril formation (l). In the present study, we attempted to determine the identity of the contents of the DFI by the use of antisera against the amyloid protein (AA) and an immuno-electron microscopic technique.Amyloidosis was induced in CBA/J mice by daily injections of casein (l). AA was isolated from amyloid-laden spleens by gel filtration and antibody to it was produced in rabbits (2). For immunocytochemistry, the unlabeled antibody enzyme method (3) was employed.

Ultrastructural analysis of collagen formation in the developing primate amnion

1990 ◽  
Vol 48 (3) ◽  
pp. 106-107
Author(s):  
Barry F. King ◽  
Grete N. Fry
Keyword(s):  
Golgi Apparatus ◽  
Collagen Fibril ◽  
Fibril Formation ◽  
Amniotic Cavity ◽  
Cytological Evidence ◽  
Mammalian Embryo ◽  
Intracellular Location ◽  
Collagen Formation ◽  
Amniotic Epithelium ◽  
Extraembryonic Mesoderm

The amnion surrounding the mammalian embryo consists of the amniotic epithelium facing the amniotic cavity, a layer of extraembryonic mesoderm bordering the exocoelom and an intervening layer of extracellular matrix (Fig. 1). During gestation the amnion expands remarkably to acommodate the rapidly growing embryo. In this study we have examined the process of collagen fibril formation in the developing amnion of the rhesus monkey between 20 and 60 days of gestation.Most cytological evidence of collagen fibril formation was observed in association with the extraembryonic mesodermal cells rather than the amniotic epithelium. The mesodermal cells h ad abundant cisternae of rough endoplasmic reticulum and a prominent Golgi apparatus. Elongated secretory vacuoles were associated with the Golgi apparatus and often contained parallel aggregates of fine filaments (Fig. 2). In some secretory vacuoles, periodic densities also were observed. Some striated collagen fibrils were observed in an apparent intracellular location in long, membrane-limited compartments (Fig. 3). Still other striated fibrils were observed in dense bodies, presumably lysosomes (Fig. 4).

Heparin induces amyloid formation in cultured human isletss

2007 ◽  
Vol 30 (4) ◽  
pp. 92 ◽  
Author(s):  
K Potter ◽  
K Park
Keyword(s):  
Cell Death ◽  
B Cells ◽  
Islet Transplantation ◽  
Islet Cell ◽  
Human Islets ◽  
Fibril Formation ◽  
Amyloid Formation ◽  
Secretory Product ◽  
Islet Amyloid ◽  
Heparin Sulfate

Background: Pancreatic islet transplantation offers improved glycemic control in type 1 diabetic patients above standard insulin therapy, ideally minimizing macro- and microvascular complications of diabetes mellitus. However success is limited thus far, with fewer than 10% of patients retaining insulin independence at two years post-transplantation. In addition to immune rejection, many non-immune factors may promote long-term graft secretory dysfunction and loss of viable graft mass. One such important non-immune factor may be the formation of islet amyloid, a pathologic lesion of the islet in type 2 diabetes that contributes to the progressive loss of b cells in that disease and that has been shown to form rapidly in human islets transplanted into NOD.scid mice. Amyloid deposits are composed primarily of the b cell secretory product islet amyloid polypeptide (IAPP), are cytotoxic, and develop in environments in which b cells are stressed. Heparin sulfate is used as an anti-coagulant in clinical islet transplantation and to prevent the instant blood-mediated inflammatory reaction (IBMIR), which occurs upon contact between islets and blood and may destroy a substantial proportion of the grafted islet mass. However, heparin is also known to stimulate amyloid fibril formation. Methods: To determine whether heparin may enhance amyloid formation in human islets and contribute to graft failure, we cultured isolated human islets in the presence or absence of heparin sulfate (42 and 420 units/ml) for 2 weeks in 11.1 mM glucose. Results: Histological assessment of sections of cultured islets for the presence of amyloid (by thioflavin S staining) revealed a marked, concentration-dependent increase in amyloid deposition following culture in the presence of heparin. Quantitative analysis of these sections showed that the proportion of islet area comprised of amyloid was increased approximately 2-fold (0.15%±0.12% vs 0.46%±0.15% of islet area) following culture in 42 units/ml heparin, and the proportion of islets in which amyloid was detectable (amyloid prevalence) was also increased (35%±24% vs 68%±10% of islets). At 420 units/ml heparin, the amyloid area was even greater (0.23%±0.15% vs 0.97%±0.42% of islet area) as was the amyloid prevalence (53%±29% vs 81%±14% of islets). To affirm that heparin can stimulate IAPP fibrillogenesis and enhance IAPP toxicity, we incubated synthetic human IAPP in the presence of heparin and measured amyloid formation in real time by thioflavin T fluorescence, and cell toxicity by Alamar blue viability assay in transformed rat (INS-1) ß-cell cultures. Heparin stimulated IAPP fibril formation and increased death of INS-1 cells exposed to IAPP (78.2%±10.9% vs 51.8%±12.2% of control viability), suggesting that heparin stimulates IAPP aggregation and toxicity. Remarkably, preliminary assessment of human islets cultured in heparin did not show increased islet cell death by TUNEL staining or loss of insulin immunostaining. Conclusion: In summary, heparin increases amyloid formation in cultured human islets. Although our preliminary data does not suggest that heparin-induced amyloid formation contributes to islet cell death, we speculate that heparin-induced amyloid formation may contribute to graft dysfunction and that caution should be used in the clinical application of this drug in islet transplantation.

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