UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Biochemical and Electrophysiological Modification of Amyloid Transthyretin on Cardiomyocytes.

Sartiani, L; Bucciantini, M; Spinelli, V; Leri, M; Natalello, A; Nosi, D; Maria Doglia, S; ... Stefani, M; + view all (2016) Biochemical and Electrophysiological Modification of Amyloid Transthyretin on Cardiomyocytes. Biophys J , 111 (9) pp. 2024-2038. 10.1016/j.bpj.2016.09.010. Green open access

[thumbnail of Bellotti_Sartiani et al.pdf]
Preview
Text
Bellotti_Sartiani et al.pdf

Download (25MB) | Preview

Abstract

Transthyretin (TTR) amyloidoses are familial or sporadic degenerative conditions that often feature heavy cardiac involvement. Presently, no effective pharmacological therapy for TTR amyloidoses is available, mostly due to a substantial lack of knowledge about both the molecular mechanisms of TTR aggregation in tissue and the ensuing functional and viability modifications that occur in aggregate-exposed cells. TTR amyloidoses are of particular interest regarding the relation between functional and viability impairment in aggregate-exposed excitable cells such as peripheral neurons and cardiomyocytes. In particular, the latter cells provide an opportunity to investigate in parallel the electrophysiological and biochemical modifications that take place when the cells are exposed for various lengths of time to variously aggregated wild-type TTR, a condition that characterizes senile systemic amyloidosis. In this study, we investigated biochemical and electrophysiological modifications in cardiomyocytes exposed to amyloid oligomers or fibrils of wild-type TTR or to its T4-stabilized form, which resists tetramer disassembly, misfolding, and aggregation. Amyloid TTR cytotoxicity results in mitochondrial potential modification, oxidative stress, deregulation of cytoplasmic Ca(2+) levels, and Ca(2+) cycling. The altered intracellular Ca(2+) cycling causes a prolongation of the action potential, as determined by whole-cell recordings of action potentials on isolated mouse ventricular myocytes, which may contribute to the development of cellular arrhythmias and conduction alterations often seen in patients with TTR amyloidosis. Our data add information about the biochemical, functional, and viability alterations that occur in cardiomyocytes exposed to aggregated TTR, and provide clues as to the molecular and physiological basis of heart dysfunction in sporadic senile systemic amyloidosis and familial amyloid cardiomyopathy forms of TTR amyloidoses.

Type: Article
Title: Biochemical and Electrophysiological Modification of Amyloid Transthyretin on Cardiomyocytes.
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.bpj.2016.09.010
Publisher version: http://dx.doi.org/10.1016/j.bpj.2016.09.010
Language: English
Additional information: © 2016. This manuscript version is published under a Creative Commons Attribution Non-commercial Non-derivative 4.0 International licence (CC BY-NC-ND 4.0). This licence allows you to share, copy, distribute and transmit the work for personal and non-commercial use providing author and publisher attribution is clearly stated. Further details about CC BY licences are available at http://creativecommons.org/licenses/by/4.0. Access may be initially restricted by the publisher.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inflammation
URI: https://discovery.ucl.ac.uk/id/eprint/1528159
Downloads since deposit
82Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item