p38 and ERK1/2 MAPKs mediate the interplay of TNF-α and IL-10 in regulating oxidative stress and cardiac myocyte apoptosis

It is known that TNF-α increases the production of ROS and decreases antioxidant enzymes, resulting in an increase in oxidative stress. IL-10 appears to modulate these effects. The present study investigated the role of p38 and ERK1/2 MAPKs in mediating the interplay of TNF-α and IL-10 in regulating oxidative stress and cardiac myocyte apoptosis in Sprague-Dawley male rats. Isolated adult cardiac myocytes were exposed to TNF-α (10 ng/ml), IL-10 (10 ng/ml), and IL-10 + TNF-α ( ratio 1) for 4 h. H2O2(100 μM) as a positive control and the antioxidant Trolox (20 μmol/l) were used to confirm the involvement of oxidative stress. H2O2treatment increased oxidative stress and apoptosis; TNF-α mimicked these effects. Exposure to TNF-α significantly increased ROS production, caused cell injury, and increased the number of apoptotic cells and Bax-to-Bcl-xl ratio. This change was associated with an increase in the phospho-p38 MAPK-to-total p38 MAPK ratio and a decrease in the phospho-ERK1/2-to-total ERK1/2 ratio. IL-10 treatment by itself had no effect on these parameters, but it prevented the above-listed changes caused by TNF-α. The antioxidant Trolox modulated TNF-α-induced changes in Bax/Bcl-xl, cell injury, and MAPKs. Preexposure of cells to the p38 MAPK inhibitor SB-203580 prevented TNF-α-induced changes. Inhibition of the ERK pathway with PD-98059 attenuated the protective role of IL-10 against TNF-α-induced apoptosis. This study provides evidence in support of the essential role of p38 and ERK1/2 MAPKs in the interactive role of TNF-α and IL-10 in cardiac myocyte apoptosis.

Download Full-text

Minocycline AttenuatesIn UteroCocaine Exposure–Induced Fetal Cardiac Myocyte Apoptosis through Inhibition of Oxidative Stress, JNK and p38 MAPK-Mediated Mitochondria-Dependent Death Pathway

10.1210/endo-meetings.2011.part2.p24.p2-77 ◽

2011 ◽

pp. P2-77-P2-77

Author(s):

Michael Mangubut ◽

Amiya P Sinha Hikim ◽

Ruoqing Shen ◽

Sushil K Mahata ◽

Indrani Sinha-Hikim

Keyword(s):

Oxidative Stress ◽

P38 Mapk ◽

Cardiac Myocyte ◽

Myocyte Apoptosis ◽

Cardiac Myocyte Apoptosis

Download Full-text

β-Adrenergic Receptor-Stimulated Cardiac Myocyte Apoptosis: Role of β1 Integrins

Journal of Signal Transduction ◽

10.1155/2011/179057 ◽

2011 ◽

Vol 2011 ◽

pp. 1-9 ◽

Cited By ~ 17

Author(s):

Parthiv Amin ◽

Mahipal Singh ◽

Krishna Singh

Keyword(s):

Cardiac Myocyte ◽

Matrix Metalloproteinase 2 ◽

Background Information ◽

Integrin Signaling ◽

Central Feature ◽

Myocyte Apoptosis ◽

Cardiac Myocyte Apoptosis

Increased sympathetic nerve activity to the myocardium is a central feature in patients with heart failure. Accumulation of catecholamines plays an important role in the pathogenesis of heart disease. Acting via β-adrenergic receptors (β-AR), catecholamines (norepinephrine and isoproterenol) increase cardiac myocyte apoptosis in vitro and in vivo. Specifically, β1-AR and β2-AR coupled to Gαs exert a proapoptotic action, while β2-AR coupled to Gi exerts an antiapoptotic action. β1 integrin signaling protects cardiac myocytes against β-AR-stimulated apoptosis in vitro and in vivo. Interaction of matrix metalloproteinase-2 (MMP-2) with β1 integrins interferes with the survival signals initiated by β1 integrins. This paper will discuss background information on β-AR and integrin signaling and summarize the role of β1 integrins in β-AR-stimulated cardiac myocyte apoptosis.

Download Full-text

Stress-Induced Changes in Testosterone Secretion in Male Rats: Role of Oxidative Stress and Modulation by Antioxidants

Open Journal of Animal Sciences ◽

10.4236/ojas.2014.42010 ◽

2014 ◽

Vol 04 (02) ◽

pp. 70-78 ◽

Cited By ~ 6

Author(s):

Mona Abdullah Al-Damegh

Keyword(s):

Oxidative Stress ◽

Male Rats ◽

Testosterone Secretion ◽

Induced Changes

Download Full-text

Burn plasma mediates cardiac myocyte apoptosis via endotoxin

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00393.2001 ◽

2002 ◽

Vol 282 (5) ◽

pp. H1907-H1914 ◽

Cited By ~ 41

Author(s):

Deborah L. Carlson ◽

Ellis Lightfoot ◽

Debora D. Bryant ◽

Sandra B. Haudek ◽

David Maass ◽

...

Keyword(s):

Primary Culture ◽

Caspase 3 ◽

Cardiac Myocyte ◽

Enzyme Linked Immunosorbent Assay ◽

Tnf Α ◽

Apoptotic Effect ◽

Myocyte Apoptosis ◽

Cardiac Myocyte Apoptosis ◽

Factor Α

Thermal trauma is associated with cardiac myocyte apoptosis in vivo. To determine whether cardiac myocyte apoptosis could be secondary to burn-induced cytokines or inflammatory mediators, we investigated the effects of tumor necrosis factor-α (TNF-α) and burn plasma on a murine cardiac myocyte cell line and primary culture myocytes. HL-1 cells were exposed to plasma isolated from burned or sham rats. Burn, but not sham plasma, induced significant increases in caspase-3 activity and DNA fragmentation. Similar results were obtained in primary culture rat myocytes. A dose-dependent increase in caspase-3 activity was observed when HL-1 cells were incubated with increasing concentrations of TNF-α. Even though TNF-α increased apoptosis, enzyme-linked immunosorbent assay detected no TNF-α in burn plasma. Burn plasma also failed to induce TNF-α mRNA, eliminating an autocrine mechanism of TNF-α secretion and binding. Also, treatment of burn plasma containing rhuTNFR:Fc failed to inhibit apoptosis. To examine the possibility that endotoxin within burn plasma might account for the apoptotic effect, burn plasma was preincubated with rBPI21. Caspase-3 activity was reduced to control levels. These data indicate that burn plasma induces apoptosis in cardiac myocytes via an endotoxin-dependent mechanism and suggest that systemic inhibition of endotoxin may provide a therapeutic approach for treatment of burn-associated cardiac dysfunction.

Download Full-text

The Long Noncoding RNA Hotair Regulates Oxidative Stress and Cardiac Myocyte Apoptosis during Ischemia-Reperfusion Injury

Oxidative Medicine and Cellular Longevity ◽

10.1155/2020/1645249 ◽

2020 ◽

Vol 2020 ◽

pp. 1-19 ◽

Cited By ~ 3

Author(s):

Kai Meng ◽

Jiao Jiao ◽

Rui-Rui Zhu ◽

Bo-Yuan Wang ◽

Xiao-Bo Mao ◽

...

Keyword(s):

Oxidative Stress ◽

Calcium Binding ◽

Cardiac Myocyte ◽

Heart Diseases ◽

Ischemia Reperfusion ◽

Negative Regulator ◽

Dependent Manner ◽

Myocyte Apoptosis ◽

Cardiac Myocyte Apoptosis

Oxidative stress and subsequent cardiac myocyte apoptosis play central roles in the initiation and progression of myocardial ischemia-reperfusion (I/R) injury. Homeobox transcript antisense intergenic RNA (Hotair) was previously implicated in various heart diseases, yet its role in myocardial I/R injury has not been clearly demonstrated. Mice with cardiac-restricted knockdown or overexpression of Hotair were exposed to I/R surgery. H9c2 cells were cultured and subjected to hypoxia/reoxygenation (H/R) stimulation to further verify the role and underlying mechanisms of Hotair in vitro. Histological examination, molecular detection, and functional parameters were determined in vivo and in vitro. In response to I/R or H/R treatment, Hotair expression was increased in a bromodomain-containing protein 4-dependent manner. Cardiac-restricted knockdown of Hotair exacerbated, whereas Hotair overexpression prevented I/R-induced oxidative stress, cardiac myocyte apoptosis, and cardiac dysfunction. Mechanistically, we observed that Hotair exerted its beneficial effects via activating AMP-activated protein kinase alpha (AMPKα). Further detection revealed that Hotair activated AMPKα through regulating the enhancer of zeste homolog 2/microRNA-451/calcium-binding protein 39 (EZH2/miR-451/Cab39) axis. We provide the evidence that endogenous lncRNA Hotair is an essential negative regulator for oxidative stress and cardiac myocyte apoptosis in myocardial I/R injury, which is dependent on AMPKα activation via the EZH2/miR-451/Cab39 axis.

Download Full-text