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ATF6 decreases myocardial ischemia/reperfusion damage and links ER stress and oxidative stress signaling pathways in the heart

RATIONALE: Endoplasmic reticulum (ER) stress causes the accumulation of misfolded proteins in the ER, activating the transcription factor, ATF6 (activating transcription factor 6 alpha), which induces ER stress response genes. Myocardial ischemia …

Junctophilin-2 gene therapy rescues heart failure by normalizing RyR2-mediated Ca2+ release

BACKGROUND: Junctophilin-2 (JPH2) is the primary structural protein for the coupling of transverse (T)-tubule associated cardiac L-type Ca channels and type-2 ryanodine receptors on the sarcoplasmic reticulum within junctional membrane complexes …

S100A4 protects the myocardium against ischemic stress

BACKGROUND: Myocardial infarction is followed by cardiac dysfunction, cellular death, and ventricular remodeling, including tissue fibrosis. S100A4 protein plays multiple roles in cellular survival, and tissue fibrosis, but the relative role of the …

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 …

PRAS40 prevents development of diabetic cardiomyopathy and improves hepatic insulin sensitivity in obesity

Diabetes is a multi-organ disease and diabetic cardiomyopathy can result in heart failure, which is a leading cause of morbidity and mortality in diabetic patients. In the liver, insulin resistance contributes to hyperglycaemia and hyperlipidaemia, …

Mechanistic target of rapamycin complex 2 protects the heart from ischemic damage

BACKGROUND: The mechanistic target of rapamycin (mTOR) comprises 2 structurally distinct multiprotein complexes, mTOR complexes 1 and 2 (mTORC1 and mTORC2). Deregulation of mTOR signaling occurs during and contributes to the severity of myocardial …

Pathological hypertrophy amelioration by PRAS40-mediated inhibition of mTORC1

Mechanistic target of rapamycin complex 1 (mTORC1), necessary for cellular growth, is regulated by intracellular signaling mediating inhibition of mTORC1 activation. Among mTORC1 regulatory binding partners, the role of Proline Rich AKT Substrate of …

Regulation of cardiac hypertrophic signaling by prolyl isomerase Pin1

RATIONALE: Cardiac hypertrophy results from the complex interplay of differentially regulated cascades based on the phosphorylation status of involved signaling molecules. Although numerous critical regulatory kinases and phosphatases have been …

New concepts of endoplasmic reticulum function in the heart: programmed to conserve

Secreted and membrane proteins play critical roles in myocardial health and disease. Studies in non-myocytes have shown that the peri-nuclear ER is the site for synthesis, folding, and quality control of most secreted and membrane proteins, as well …

ATF6 [corrected] and thrombospondin 4: the dynamic duo of the adaptive endoplasmic reticulum stress response