Periostin, the distribution and expression of which were consistent with the extent of myocardial fibrosis, might be a potential biomarker of cardiac remodeling in heart failure patients.

Curcumin, which is the effective component of turmeric (Curcuma longa), has previously been shown to exert potent antioxidant, antitumor and anti‑inflammatory activities in vitro and in vivo. However, the mechanism underlying the protective effects of curcumin against oxidative damage in endothelial cells remains unclear. The present study aimed to examine the effects of curcumin on hydrogen peroxide (H2O2)‑induced apoptosis and autophagy in EA.hy926 cells, and to determine the underlying molecular mechanism. Cultured EA.hy926 cells were treated with curcumin (5‑20 µmol/l) 4 h prior to and for 4 h during exposure to H2O2 (200 µmol/l). Oxidative stress resulted in a significant increase in the rate of cell apoptosis, which was accompanied by an increase in the expression levels of caspase‑3 and B‑cell lymphoma 2 (Bcl‑2)‑associated X protein (Bax), and a decrease in the expression levels of Bcl‑2. Treatment with curcumin (5 or 20 µmol/l) significantly inhibited apoptosis, and reversed the alterations in caspase‑3, Bcl‑2 and Bax expression. Furthermore, curcumin induced autophagy and microtubule‑associated protein 1A/1B‑light chain 3‑Ⅱ expression, and suppressed the phosphorylation of Akt and mammalian target of rapamycin (mTOR). These results indicated that curcumin may protect cells against oxidative stress‑induced damage through inhibiting apoptosis and inducing autophagy via the Akt/mTOR pathway.

The cardiotoxicity of doxorubicin limits its clinical use in the treatment of a variety of solid tumors and malignant hematologic disease. Although the mechanism by which it causes cardiac injury is not yet known, apoptosis has been regarded as one of mechanisms underlying the cardiotoxic effects of doxorubicin. Eukaryotic translation initiation factor 5A (eIF5A) is a ubiquitously expressed multifunctional protein that interacts with a range of ligands and is implicated in cell signaling. However, there has been no direct evidence for the critical involvement of eIF5A in doxorubicin-induced apoptosis. Overexpression of eIF5A induced by doxorubicin in cardiomyocyte leads to growth perturbation along with initiation of apoptosis. Overexpression of eIF5A results in a gradual increase in reactive oxygen species (ROS) generation. This mitochondrial dysfunction is due to a gradual increase in ROS generation in eIF5A-overexpressing H9c2 cells. Along with ROS generation, increased Ca(2+) influx in mitochondria leads to loss of the mitochondrial transmembrane potential, release of cytochrome-c, and caspase activation. However, small interfering RNA (siRNA)-mediated suppression of eIF5A results in inhibition of apoptosis. Interestingly, upon overexpression of eIF5A induced by doxorubicin, cell apoptosis was shown to be significantly inhibited when cells were treated with SB202190 (p38 mitogen-activated protein kinase inhibitor) and SP600125 (anti-c-Jun N-terminal kinase inhibitor) for 18 h. The reduction in oxidant generation and reduction in the apoptotic cell population were the results of the disruption of eIF5A expression, corroborating the hypothesis that excess ROS generation with overexpression of eIF5A induced by doxorubicin leads to apoptosis due to the accumulation of eIF5A.

No abstract