[Cytotoxicity of amyloid fibrils of X-protein].
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.
Marsagishvili
L G
LG
Shpagina
M D
MD
Shatalin
Iu V
IuV
Shubina
V S
VS
Naumov
A A
AA
Potselueva
M M
MM
Podlubnaia
Z A
ZA
D000682:Amyloid / Q000737:chemistry / Q000502:physiology* / Q000633:toxicity; D000818:Animals; D002470:Cell Survival; D002478:Cells, Cultured; D064211:Connectin; D008854:Microscopy, Electron; D009124:Muscle Proteins / Q000502:physiology* / Q000633:toxicity; D018482:Muscle, Skeletal / Q000737:chemistry; D009504:Neutrophils / Q000166:cytology; D011494:Protein Kinases / Q000502:physiology* / Q000633:toxicity; D011817:Rabbits; D051381:Rats; D013752:Tetracycline / Q000494:pharmacology
D000682:Amyloid; D064211:Connectin; D009124:Muscle Proteins; D011494:Protein Kinases; D013752:Tetracycline