Cytotoxicity of amyloid fibrils of X-protein

• Published in: Biofizika Vol. 51; no. 5; p. 799
• Main Authors: Marsagishvili, L G, Shpagina, M D, Shatalin, Iu V, Shubina, V S, Naumov, A A, Potselueva, M M, Podlubnaia, Z A
• Format: Journal Article
• Language: Russian
• Published: Russia (Federation) 01.09.2006
• Subjects: Amyloid - chemistry; Amyloid - physiology; Amyloid - toxicity; Animals; Cell Survival; Cells, Cultured; Connectin; Microscopy, Electron; Muscle Proteins - physiology; Muscle Proteins - toxicity; Muscle, Skeletal - chemistry; Neutrophils - cytology; Protein Kinases - physiology; Protein Kinases - toxicity; Rabbits; Rats; Tetracycline - pharmacology
• ISSN: 0006-3029

It is known that amyloid oligomers, protofibrils, and fibrils induce cell death, and antibiotic tetracycline inhibits the fibrillization of beta amyloid peptides and other amyloidogenic proteins and disassembles their pre-formed fibrils. Earlier we have demonstrated that sarcomeric cytoskeletal proteins of the titin family (X-, C-, and H-proteins) are capable to form in vitro amyloid fibrils, and tetracycline effectively destroys these fibrils. Here we show that the viability of polymorphonuclear leukocytes in the presence of X-protein amyloids depends on the concentration of amyloid fibrils of X-protein and the time of incubation. In addition to the disaggregation of X-protein fibrils, tetracycline eliminated the cytotoxic effect of the protein. The antibiotic itself did not show a toxic effect, and the cell viability in its presence even increased. Our results evidence the potential of this approach for evaluating the effectiveness of drugs preventing or treating amyloidoses.