Role In Cardiac Cells Research Articles

CARDIOPROTECTIVE POTENTIAL OF QUERCETIN AGAINST DIESEL OR PETROL EXHAUST NANOPARTICLE INDUCED TOXICITY: A PROSPECTIVE IN VITRO PHARMACOLOGICAL STUDY IN H9C2 CELLS

Objective: Phytochemicals are known to elicit potential antioxidant activity. This study examined the cardioprotective effects of quercetin against oxidative damage to rat cardiomyocyte cells (H9c2) after treatment with Diesel Exhaust Nanoparticles (DEPs) or Petrol Exhaust Nanoparticles (PEPs).
 Methods: Cardiomyocyte cells were exposed to DEPs or PEPs alone and in a combination with quercetin for 24 h.
 Results: Results showed that quercetin had no lethal effect on H9c2 cells up to a concentration of 1.0 μg/ml. Exposure to DEPs (4.0 μg/ml) or PEPs (10.0 μg/ml) induced cytotoxicity, oxidative stress, and inflammation (p<0.05). It also provoked lipid peroxidation by an increase in MDA and a decrease in SOD activity and glutathione activity (p<0.05). Simultaneous addition of quercetin restored these parameters to near normal.
 Conclusion: These results thus specify that quercetin plays a protective role in cardiac cells exposed to DEPs and PEPs.

Modulation of apoptosis by sulforaphane is associated with PGC-1α stimulation and decreased oxidative stress in cardiac myoblasts.

Sulforaphane is a naturally occurring isothiocyanate capable of stimulating cellular antioxidant defenses and inducing phase 2 detoxifying enzymes, which can protect cells against oxidative damage. Oxidative stress and apoptosis are intimately involved in the pathophysiology of cardiac diseases. Although sulforaphane is known for its anticancer benefits, its role in cardiac cells is just emerging. The aim of the present study was to investigate whether sulforaphane can modulate oxidative stress, apoptosis, and correlate with PGC-1α, a transcriptional cofactor involved in energy metabolism. H9c2 cardiac myoblasts were incubated with R-sulforaphane 5µmol/L for 24h. Cell viability, ANP gene expression, oxidative stress and apoptosis markers, and protein expression of PGC-1α were studied. In cells treated with sulforaphane, cellular viability increased (12%) and ANP gene expression decreased (46%) compared to control cells. Moreover, sulforaphane induced a significant increase in superoxide dismutase (103%), catalase (101%), and glutathione S-transferase (72%) activity, reduced reactive oxygen species levels (15%) and lipid peroxidation (65%), as well as stimulated the expression of the cytoprotective enzyme heme oxygenase-1 (4-fold). Sulforaphane also promoted an increase in the expression of the anti-apoptotic protein Bcl-2 (60%), decreasing the Bax/Bcl-2 ratio. Active Caspase 3\7 and p-JNK/JNK were also reduced by sulforaphane, suggesting a reduction in apoptotic signaling. This was associated with an increased protein expression of PGC-1α (42%). These results suggest that sulforaphane offers cytoprotection to cardiac cells by activating PGC1-α, reducing oxidative stress, and decreasing apoptosis signaling.

Bitter taste receptor agonists elicit G-protein-dependent negative inotropy in the murine heart.

G-protein-coupled receptors (GPCRs) are key mediators in cardiovascular physiology, yet frontline therapies for heart disease target only a small fraction of the cardiac GPCR repertoire. Moreover, there is emerging evidence that GPCRs implicated in taste (Tas1r and Tas2rs) have specific functions beyond the oral cavity. Our recent description of these receptors in heart tissue foreshadows a potential novel role in cardiac cells. In this study, we identified novel agonist ligands for cardiac-Tas2rs to enable the functional investigation of these receptors in heart tissue. Five Tas2rs cloned from heart tissue were screened against a panel of 102 natural or synthetic bitter compounds in a heterologous expression system. We identified agonists for Tas2r108, Tas2r137, and Tas2r143 that were then tested in Langendorff-perfused mouse hearts (from 8-wk-old male C57BL/6 mice). All Tas2r agonists tested exhibited concentration-dependent effects, with agonists for Tas2r108 and Tas2r137, leading to a ∼40% decrease in left ventricular developed pressure and an increase in aortic pressure, respectively. These responses were abrogated in the presence of Gαi and Gβγ inhibitors (pertussis toxin and gallein). This study represents the first demonstration of profound Tas2r agonist-induced, G protein-dependent effects on mouse heart function.

A New State of Myosin in Cardiac Muscles with Very Slow ATP Turnover: A Potential Cardio-Protective Mechanism in the Heart

We used quantitative epi-fluorescence of mant-nucleotides to measure single nucleotide turnovers in small bundles of permeable rabbit ventricle cells. In relaxed cells nucleotide turnover occurs in two phases one with a short time constant, 14 ± 1 seconds, and a second with a much longer time constant, 144 ± 10 seconds. The first is compatible with the normal relaxed state and the second arises from myosin heads in the Super Relaxed State (SRX). Approximately 60% of the myosin heads were in the SRX. Recent work identified a similar state with a slow nucleotide turnover time constant, 230 seconds, in relaxed vertebrate skeletal muscle (Stewart et.al. PNAS, 2010). The SRX appears to play a similar role in relaxed skeletal fibers and cardiac cells providing a state with a very low metabolic rate. However, in active fibers the properties of the SRX differ dramatically. There is a rapid transition of myosin heads out of the SRX in active skeletal fibers. In contrast, in cardiac muscle, the population of myosin heads in the SRX is not changed when the muscle, is activated. This property allows the SRX to play a very different role in cardiac cells than in skeletal fibers. The mechanisms that control cardiac contractility are complex, leading to an output that can vary from highly active to very quiescent. The ability of myosin heads to remain in the SRX, while other heads are generating tension, allows this state to play a role in the regulation of cardiac output. In particular, the super relaxed state could provide a mechanism for decreasing the metabolic load on the heart, being cardioprotective, particularly in time of stress such as ischemia.

Regulation of cardiomyocyte growth by the cAMP-binding protein Epac

Cyclic AMP (cAMP) plays a critical role in the heart because it regulates many physiological processes. The recent discovery of Epac (Exchange Protein directly Activated by cAMP), that functions independently of PKA, raises the question of its role in cardiac cells. There are two variants of Epac, Epac1 and Epac2, both are characterized by a regulatory domain which binds directly cAMP and a catalytic region containing an exchange factor motif for the Ras-like small GTPases Rap. Here, we investigated Epac isoform expression in human failing hearts and the functional effect of Epac in adult rat ventricular cardiomyocytes (ARVC).