Altered calcium regulation in isolated cardiomyocytes from Egr-1 knock-out mice

Abstract

Early growth response-1 one gene (Egr-1), one of the immediate early response genes, plays an important role in the adaptive response of the myocardium to hypertrophic stimuli. We aimed to investigate the effects of Egr-1 deletion on cardiac function. Egr-1 knock-out (Egr-1(-/-)) homozygous mice were employed to evaluate the electrophysiological and molecular properties of left ventricular cardiomyocytes (VCM) by using patch-clamp technique, intracellular calcium measurements, real-time PCR, and Western blot. Action potential was prolonged and diastolic potential was positive-shifted in VCMs isolated from Egr-1(-/-) mice, in comparison with those from their wild-type (WT) littermates. The calcium content of the sarcoplasmic reticulum was reduced and the decay time for steady-state calcium transient slowed down. Serca2, Ryr, L-type Ca(2+)-channel, and PLB mRNA expression were reduced in Egr-1(-/-) mice compared with the controls. Moreover, Serca2 protein was reduced, while the amount of Ncx1 protein was increased in Egr-1(-/-) hearts compared with those of the WT littermates. Furthermore, genes involved in heart development (GATA-4, TGF-β) and in Egr-1 regulation (Nab1, Nab2) were down regulated in Egr-1(-/-) mice. These results suggest that Egr-1 plays a pivotal role in regulating excitation-contraction coupling in cardiac myocytes.

Defects in calcium homeostasis and mitochondria can be reversed in Pompe disease

“…[41][42][43]65,66 In addition, our gene expression studies showed upregulation of 2 members of the early growth response gene (Egr) family, in particular Egr1 (4.25-fold) in the KO muscle; Egr1 is a physiological regulator of genes involved in calcium handling including L-type Ca 2C channel. 67 We reasoned that the increased CACNB1 in Pompe muscle cells triggers the observed surge in cytosolic Ca 2C levels and mitochondrial Ca 2C overload-a condition which is exacerbated with age of the animal and is not resolved by treatment with the therapeutic enzyme. An increase in Ca 2C levels in Pompe cells could lead to the increased autophagy, but this relationship is a subject of controversy.…”

Effects of ranolazine in a model of doxorubicin‐induced left ventricle diastolic dysfunction

“…Adult rat left ventricular myocytes (ARVM) were obtained from 3-month-old rats (Pacini et al, 2013;Ferrantini et al, 2014). Animal studies were performed according to the University of Florence laboratory animal guidelines.…”

Loss of Egr-1 sensitizes pancreatic β-cells to palmitate-induced ER stress and apoptosis

“…Furthermore, Egr-1 deficiency is very sensitive to the perturbation of intracellular calcium homeostasis, because only treatment of Egr-1 knockdown cells with thapsigargin, which inhibits SERCA leading to calcium depletion in ER, causes further increases in ER stress and cell death. Altered calcium regulation has been found in Egr1 −/− cardiomyocytes through downregulation of major proteins involved in control of calcium homeostasis [35,36]. Thus, we speculate that attenuation of ER stress by Egr-1 in β-cells may mediate through remodeling of calcium homeostasis.…”