elastin and Amyloidosis

Topics: Amyloid; Amyloidosis; Birefringence; Bone and Bones; Capillaries; Cell Membrane; Clinical Laboratory Techniques; Collagen; Dental Enamel; Dentin; Elastin; Erythrocytes; Humans; Microscopy, Polarization; Nerve Tissue; Neuroglia; Neurons; Nucleoproteins; Rectum; Reticulin; Skin; Spleen

The main aim of this study is to better understand the self-aggregation mechanism of amyloid-like elastin-derived fibers in order to design and produce new powerful drugs that will inhibit the onset of 'amyloidosis'.. Atomic force microscopy (AFM), Congo Red birefringence assay and Thioflavin T fluorescence measurements were used to demonstrate the amyloid-like behavior of some fragments of elastin protein (exon 30 [EX30] and exon 28 [EX28]). Turbidimetry on apparent absorbance technique was used to investigate the effect either of enhancers or of inhibitors on the amyloidogenic elastin-like peptides. Circular-dichroism spectroscopy was used to study the secondary structures of the peptides.. We used Congo Red birefringence assay, Thioflavin T fluorescence measurements and AFM measurements that are used commonly to demonstrate the formation of amyloids. The elastin fibrillogenesis is amyloid-like. Then, the elastin amyloidogenesis is inhibited by particular pentapeptides.. We have reported herein that the fibrillogenesis of elastin-derived EX28 and EX30 polypeptides is facilitated significantly by the effect of sodium taurocholate bile salt and is inhibited by a classical inhibitor of Abeta-amyloid peptide, such as KLVFF, as well as by novel inhibitors, designed by us on the basis of some elastin sequences.

Topics: Amyloid; Amyloid beta-Peptides; Amyloidosis; Elastin; Humans; Peptide Fragments; Peptides; Taurocholic Acid; Temperature; Time Factors

We describe 13 cases in which the submucosa and muscularis mucosae of the gastrointestinal tract exhibited a focal or diffuse increase of elastin fibers. This elastosis or elastofibromatous change most commonly manifested as a colonic polyp and usually was found during screening colonoscopy. Gastric and small intestinal cases were less frequent and associated with ulcers or an inflammatory process. The literature includes reports of 13 gastrointestinal elastotic lesions with a topographic distribution similar to that in our series. Histologically, elastosis appears as finely granular and/or fibrillar amphophilic material, sometimes with a fibrous component (elastofibromatous change). The changes occasionally appear centered around blood vessels and often are mistaken for amyloid but are negative for Congo red stain and strongly positive for elastin stain. We believe that this lesion might be more underrecognized than rare. In 2 of 26 cases, elastotic lesions also were present in nongastrointestinal sites.

Topics: Aged; Aged, 80 and over; Amyloidosis; Colonic Polyps; Colonoscopy; Diagnosis, Differential; Elastic Tissue; Elastin; Female; Gastrointestinal Diseases; Humans; Male; Middle Aged; Prospective Studies

Topics: Amyloidosis; Bronchial Diseases; Elastin; Fibroma; Humans; Tracheal Diseases

The multifunctional glycoprotein vitronectin, also called serum spreading factor and S-protein of complement, is a potent inducer of cell adhesion and spreading in vitro, and also has a regulatory function in the complement and coagulation pathways. It is present both in plasma and tissue. Recently, vitronectin immunoreactivity was demonstrated in the elastic fibres of normal human skin. Normal and amyloid kidney tissue was investigated for vitronectin immunoreactivity using polyclonal and monoclonal antibodies in an avidin-biotin-peroxidase complex technique and in an alkaline phosphatase anti-alkaline phosphatase complex technique. Vitronectin was found in the elastic layers of normal vessel walls, and in glomerular sclerotic lesions in cases of benign nephrosclerosis, but not in normal glomeruli. Strong specific vitronectin immunoreactivity was found in the amyloid deposits in kidneys from cases with amyloid A type amyloidosis, and in cases with amyloid light chain type amyloidosis. Structures immunostainable with anti-amyloid A antiserum were invariably immunostainable with anti-vitronectin. An antiserum against serum amyloid P component stained the same structures as did the anti-vitronectin antibodies, and in addition stained normal glomerular basement membranes. In conclusion, vitronectin immunoreactivity was demonstrated in elastic tissue, in amyloid deposits and in sclerotic lesions in human kidney.

Topics: Amyloid; Amyloidosis; Blood Proteins; Elastin; Female; Glycoproteins; Humans; Immunoenzyme Techniques; Kidney; Male; Middle Aged; Vitronectin

Amyloid deposits almost invariably contain a pentagonal-shaped protein (a so-called pentraxin), termed amyloid P component (AP), in close apposition to the amyloid fibrils. AP is also detected alongside normal elastin fibres in skin and basement membrane. In the present studies, purified human AP was shown to inhibit the activity of porcine pancreatic elastase. The inhibition of elastolytic activity was not abolished by heating AP to 70 degrees C. Furthermore, two other human serum proteins used as controls did not inhibit elastase activity: albumin, which has a similarly acidic pI, and C-reactive protein, which is a pentraxin, sharing 50% sequence homology with AP. Enzyme kinetic studies showed that elastase treated with AP had a slower elastolytic rate than untreated elastase. The inhibitory effect of AP was reversed by high substrate (fivefold) concentration. These observations suggest that AP may function in vivo to protect elastin and amyloid fibrils from proteolytic cleavage. Indeed, this may in part account for the relative resistance of amyloid deposits to resorption and proteolysis.

Topics: Amyloid; Amyloidosis; Animals; Chemical Phenomena; Chemistry; Drug Interactions; Elastin; Humans; Pancreas; Pancreatic Elastase; Serum Amyloid P-Component; Swine

Topics: Amino Acids; Amyloidosis; Collagen; Elastic Tissue; Elastin; Epidermolysis Bullosa; Epidermolysis Bullosa Acquisita; Geriatrics; Hexosamines; Histocytochemistry; Humans; Pathology; Skin