A FTIR microspectroscopy study of the structural and biochemical perturbations induced by natively folded and aggregated transthyretin in HL-1 cardiomyocytes.
Sci Rep
; 8(1): 12508, 2018 08 21.
Article
en En
| MEDLINE
| ID: mdl-30131519
ABSTRACT
Protein misfolding and aggregation are associated with a number of human degenerative diseases. In spite of the enormous research efforts to develop effective strategies aimed at interfering with the pathogenic cascades induced by misfolded/aggregated peptides/proteins, the necessary detailed understanding of the molecular bases of amyloid formation and toxicity is still lacking. To this aim, approaches able to provide a global insight in amyloid-mediated physiological alterations are of importance. In this study, we exploited Fourier transform infrared microspectroscopy, supported by multivariate analysis, to investigate in situ the spectral changes occurring in cultured intact HL-1 cardiomyocytes exposed to wild type (WT) or mutant (L55P) transthyretin (TTR) in native, or amyloid conformation. The presence of extracellular deposits of amyloid aggregates of WT or L55P TTR, respectively, is a key hallmark of two pathological conditions, known as senile systemic amyloidosis and familial amyloid polyneuropathy. We found that the major effects, associated with modifications in lipid properties and in the cell metabolic/phosphorylation status, were observed when natively folded WT or L55P TTR was administered to the cells. The effects induced by aggregates of TTR were milder and in some cases displayed a different timing compared to those elicited by the natively folded protein.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Prealbúmina
/
Miocitos Cardíacos
/
Mutación
Límite:
Humans
Idioma:
En
Revista:
Sci Rep
Año:
2018
Tipo del documento:
Article
País de afiliación:
Italia