Targeting unfolded protein response reverts ER stress and ER Ca²⁺ homeostasis in cardiomyocytes expressing the pathogenic variant of Lamin A/C R321X.

ABSTRACT:

Background

We previously demonstrated that an Italian family affected by a severe dilated cardiomyopathy (DCM) with history of sudden deaths at young age, carried a mutation in the Lmna gene encoding for a truncated variant of the Lamin A/C protein (LMNA), R321X. When expressed in heterologous systems, such variant accumulates into the endoplasmic reticulum (ER), inducing the activation of the PERK-CHOP pathway of the unfolded protein response (UPR), ER dysfunction and increased rate of apoptosis. The aim of this work was to analyze whether targeting the UPR can be used to revert the ER dysfunction associated with LMNA R321X expression in HL-1 cardiac cells.

Methods

HL-1 cardiomyocytes stably expressing LMNA R321X were used to assess the ability of 3 different drugs targetin

SUBMITTER: Pietrafesa G 

PROVIDER: S-EPMC10204200 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature