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ATF6 protects against protein misfolding during cardiac hypertrophy

Cardiomyocytes activate the unfolded protein response (UPR) transcription factor ATF6 during pressure overload-induced hypertrophic growth. The UPR is thought to increase ER protein folding capacity and maintain proteostasis. ATF6 deficiency during …

mTORC1 inhibition impairs activation of the unfolded protein response and induces cell death during ER stress in cardiomyocytes

The mechanistic target of rapamycin complex 1 (mTORC1) is a central regulator of protein synthesis that senses and responds to a variety of stimuli to coordinate cellular metabolism with environmental conditions. To ensure that protein synthesis is …

Proteomic analysis of the cardiac myocyte secretome reveals extracellular protective functions for the ER stress response

The effects of ER stress on protein secretion by cardiac myocytes are not well understood. In this study, the ER stressor thapsigargin (TG), which depletes ER calcium, induced death of cultured neonatal rat ventricular myocytes (NRVMs) in high media …

Monitoring cell-type-specific gene expression using ribosome profiling in vivo during cardiac hemodynamic stress

RATIONALE: Gene expression profiles have been mainly determined by analysis of transcript abundance. However, these analyses cannot capture posttranscriptional gene expression control at the level of translation, which is a key step in the regulation …

Hrd1 and ER-associated protein degradation, ERAD, are critical elements of the adaptive ER stress response in cardiac myocytes

RATIONALE: Hydroxymethyl glutaryl-coenzyme A reductase degradation protein 1 (Hrd1) is an endoplasmic reticulum (ER)-transmembrane E3 ubiquitin ligase that has been studied in yeast, where it contributes to ER protein quality control by ER-associated …

Ischemia activates the ATF6 branch of the endoplasmic reticulum stress response

Stresses that perturb the folding of nascent endoplasmic reticulum (ER) proteins activate the ER stress response. Upon ER stress, ER-associated ATF6 is cleaved; the resulting active cytosolic fragment of ATF6 translocates to the nucleus, binds to ER …