H2O2-induced secretion of tumor necrosis factor-α evokes apoptosis of cardiac myocytes through reactive oxygen species-dependent activation of p38 MAPK

Abstract

P38 mitogen-activated protein kinases (p38 MAPK) and tumor necrosis factor-a (TNF-a) play important roles in oxidative stress-induced apoptosis in cardiac myocytes. However, the regulation and functional role of cross-talk between p38 MAPK and TNF-a pathways have not yet been fully characterized in cardiac myocytes. In this study, we found that inhibition of p38 MAPK with SB-203580 (SB) reduced H 2 O 2 -stimulated secretion of TNF-a, whereas pre-activation of p38 MAPK with sodium arsenite (SA) enhanced H 2 O 2 -stimulated secretion of TNF-a. In addition, pretreatment of cells with TNF-a increased basal and H 2 O 2 -stimulated p38 MAPK and apoptosis of cardiac myocytes, and p38 MAPK-associated apoptosis of cardiac myocytes induced by TNF-a was blocked by inhibition of p38 MAPK with SB. Finally, H 2 O 2 -induced apoptosis was attenuated by the inhibitors of p38 MAPK or reactive oxygen species (ROS), whereas it was enhanced by p38 MAPK agonist SA. These results suggest that H 2 O 2 -induced secretion of TNF-a increases apoptosis of cardiac myocytes through ROS-dependent activation of p38 MAPK. This may represent a novel mechanism that TNF-a partly interplays with p38 MAPK pathways during oxidative stress-modulated apoptosis in cardiac myocytes.

Baicalin potentiates TRAIL-induced apoptosis through p38 MAPK activation and intracellular reactive oxygen species production

“…Consistently, our previous study demonstrated that wogonin, another important component of S. baicalensis Georgi, activates ROS to promote TRAIL-induced apoptosis (13). It is also known that the activation of p38 is often mediated by ROS (19)(20)(21)(22). However, the results of the present study revealed that baicalin and TRAIL-induced activation of p38 is independent of ROS.…”

β1‐adrenergic receptor autoantibodies from heart failure patients enhanced TNF‐α secretion in RAW264.7 macrophages in a largely PKA‐dependent fashion

“…cardiomyocyte apoptosis [Chen et al, 2012]. Our results suggest that both b 1 -AA-positive and -negative IgGs might directly activate RAW264.7 cells and promote the secretion of TNF-a, though the effect of b 1 -AA-positive IgGs was more pronounced than that of b 1 -AA-negative IgGs.…”

The Potential Protective Role of Vitamin E and Selenium against Sub-chronic Toxicity of Hexavalent Chromium on the Testis of Adult Male Albino Rats

“…Aruldhas et al (2005) supported these results as they stated that direct interaction of reactive chromium intermediates with DNA leading to DNAchromium binding, DNA-protein crosslinks and DNA-DNA crosslinks and they added that interaction of chromium with GSH results in strand breaks and chromium-DNA binding. Chen et al (2012) attributed the DNA damage to the reactive oxygen species ROS that can convert fatty acids to toxic lipid peroxides and could damage every major cellular component.…”