Chaperones and cardiac misfolding protein diseases.

Abstract:

:Cardiomyocytes are best known for their spontaneous beating activity, large cell size, and low regenerative capacity during adulthood. The mechanical activity of cardiomyocytes depends on a sophisticated contractile apparatus comprised of sarcomeres whose rhythmic contraction relies on Ca(2+) transients with a high level of energy consumption. Hence the proper folding and assembly of the sarcomeric and other accessory proteins involved in those diverse functions (i.e., structural, mechanical, energy exchange and production) is critical for muscle mechanics. Chaperone proteins assist other polypeptides to reach their proper conformation, activity and/or location. Consequently, chaperone-like functions are important for the healthy heart but assume greater relevance during cardiac diseases when such chaperone proteins are recruited: 1) to protect cardiac cells against adverse effects during the pathological transition, and 2) to mitigate certain pathogenic mechanisms per se. Protein misfolding is observed as a consequence of inappropriate intracellular environment with acquired conditions (e.g., ischemia/reperfusion and redox imbalance) or because of mutations, which can modify primary to quaternary protein structures. In this review, we discuss the importance of cardiac chaperones while emphasizing the genetic origin (modification of gene/protein sequence) of cardiac protein misfolding and their consequences on the cardiomyocytes leading to organ dysfunction and failure.

journal_name

Curr Protein Pept Sci

authors

Christians ES,Mustafi SB,Benjamin IJ

doi

10.2174/1389203715666140331111518

subject

Has Abstract

pub_date

2014-05-01 00:00:00

pages

189-204

issue

3

eissn

1389-2037

issn

1875-5550

pii

CPPS-EPUB-59870

journal_volume

15

pub_type

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