Hypoxia, angiotensin‐II, and norepinephrine mediated apoptosis is stimulus specific in canine failed cardiomyocytes: a role for p38 MAPK, Fas‐L and cyclin D<sub>1</sub>

Sharov, Victor G.; Todor, Anastassia; Suzuki, George; Morita, Hideaki; Tanhehco, Elaine J.; Sabbah, Hani N.

doi:10.1016/s1388-9842(02)00254-4

Cited by 43 publications

(25 citation statements)

References 19 publications

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“…In the infarct heart, cytokines such as tumor necrosis factor and interleukin 6 and injury of ischemia‐reperfusion activate the p38 signaling pathway 26. Furthermore, as a critical part of the response to MI in the heart, several investigations have confirmed that the p38 pathway sensitizes the caspase cascade to induce cell apoptosis, which supports our findings 27, 28. We observed that the activation of p38 was attenuated by knockdown of TGFβR3 under H 2 O 2 or MI conditions.…”

Section: Discussionsupporting

confidence: 87%

Transforming Growth Factor‐β Receptor III is a Potential Regulator of Ischemia‐Induced Cardiomyocyte Apoptosis

Sun

Duan

et al. 2017

JAHA

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BackgroundMyocardial infarction (MI) is often accompanied by cardiomyocyte apoptosis, which decreases heart function and leads to an increased risk of heart failure. The aim of this study was to examine the effects of transforming growth factor‐β receptor III (TGFβR3) on cardiomyocyte apoptosis during MI.Methods and ResultsAn MI mouse model was established by left anterior descending coronary artery ligation. Cell viability, apoptosis, TGFβR3, and mitogen‐activated protein kinase signaling were assessed by methylthiazolyldiphenyl‐tetrazolium bromide assay, terminal deoxynucleotidyl transferase‐mediated dUTP nick end labeling assay, immunofluorescence, electron microscopy, and Western blotting. Our results demonstrated that TGFβR3 expression in the border region of the heart was dynamically changed during MI. After stimulation with H2O2, TGFβR3 overexpression in cardiomyocytes led to increased cell apoptosis and activation of p38 signaling, whereas TGFβR3 knockdown had the opposite effect. ERK1/2 and JNK1/2 signaling was not altered by TGFβR3 modulation, and p38 inhibitor (SB203580) reduced the effect of TGFβR3 on apoptosis, suggesting that p38 has a nonredundant function in activating apoptosis. Consistent with the in vitro observations, cardiac TGFβR3 transgenic mice showed augmented cardiomyocyte apoptosis, enlarged infarct size, increased injury, and enhanced p38 signaling upon MI. Conversely, cardiac loss of function of TGFβR3 by adeno‐associated viral vector serotype 9–TGFβR3 short hairpin RNA attenuated the effects of MI in mice.Conclusions TGFβR3 promotes apoptosis of cardiomyocytes via a p38 pathway–associated mechanism, and loss of TGFβR3 reduces MI injury, which suggests that TGFβR3 may serve as a novel therapeutic target for MI.

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Section: Discussionsupporting

confidence: 87%

Transforming Growth Factor‐β Receptor III is a Potential Regulator of Ischemia‐Induced Cardiomyocyte Apoptosis

Sun

Duan

et al. 2017

JAHA

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“…10,11 Another group showed that hypoxia-, angiotensin II-, and norepinephrine-mediated canine cardiac myocyte apoptosis is dependent on p38 MAPK activity. 12 The specific targets of p38 MAPK that are important for a proapoptotic response are not completely known but may include the transcription factor p53. It is not clear whether p38 MAPK-mediated p53 phosphorylation is important in cardiac myocyte apoptosis, but our results suggest that inhibition of p38 MAPK in human patients may be a useful method to ameliorate cardiac myocyte death in response to provocative stimulation such as ischemia or pressure overload.…”

Section: Discussionmentioning

confidence: 99%

Role of 14-3-3-Mediated p38 Mitogen-Activated Protein Kinase Inhibition in Cardiac Myocyte Survival

Zhang

Ren

Zhang

et al. 2003

Circulation Research

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14-3-3 family members are dimeric phosphoserinebinding proteins that regulate signal transduction, apoptotic, and checkpoint control pathways. Targeted expression of dominant-negative 14-3-3 (DN-14-3-3) to murine postnatal cardiac tissue potentiates Ask1, c-jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase (MAPK) activation. DN-14-3-3 mice are unable to compensate for pressure overload, which results in increased mortality, dilated cardiomyopathy, and cardiac myocyte apoptosis. To evaluate the relative role of p38 MAPK activity in the DN-14-3-3 phenotype, we inhibited cardiac p38 MAPK activity by pharmacological and genetic methods. Intraperitoneal injection of SB202190, an inhibitor of p38␣ and p38␤ MAPK activity, markedly increased the ability of DN-14-3-3 mice to compensate for pressure overload, with decreased mortality. DN-14-3-3 mice were bred with transgenic mice in which dominant-negative p38␣ (DN-p38␣) or dominantnegative p38␤ (DN-p38␤) MAPK expression was targeted to the heart. Compound transgenic DN-14-3-3/DNp38␤ mice, and to a lesser extent compound transgenic DN-14-3-3/DN-p38␣ mice, exhibited reduced mortality and cardiac myocyte apoptosis in response to pressure overload, demonstrating that DN-14-3-3 promotes cardiac apoptosis due to stimulation of p38 MAPK activity.

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“…In vitro treatment with a p38 inhibitor, mainly SB203580, prior to ischemia at concentrations ranging from 1 to 15 μM was found to protect the cardiac cells from ischemia/reperfusion injury, suggesting an undesired effect of p38 activation in myocardial ischemia/reperfusion [36,50,[54][55][56][57][58][59][60][61][62][63]. However, there have been some reports of beneficial effects following p38 activation, in which its activation could lead to the protection against injury rather than a harmful effect.…”

Section: Reports Of P38 Inhibitor In An In Vitro Model Of Ischemia/rementioning

confidence: 99%

Role of p38 inhibition in cardiac ischemia/reperfusion injury

Kumphune

Chattipakorn

2011

Eur J Clin Pharmacol

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The p38 mitogen-activated protein kinases (p38s) are Ser/Thr kinases that are activated as a result of cellular stresses and various pathological conditions, including myocardial ischemia/reperfusion. p38 activation has been shown to accentuate myocardial injury and impair cardiac function. Inhibition of p38 activation and its activity has been proposed to be cardioprotective by slowing the rate of myocardial damage and improving cardiac function. The growing body of evidence on the use of p38 inhibitors as therapeutic means for responding to heart problems is controversial, since both beneficial as well as a lack of protective effects on the heart have been reported. In this review, the outcomes from studies investigating the effect of p38 inhibitors on the heart in a wide range of study models, including in vitro, ex vivo, and in vivo models, are discussed. The correlations of experimental models with practical clinical usefulness, as well as the need for future studies regarding the use of p38 inhibitors, are also addressed.

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Hypoxia, angiotensin‐II, and norepinephrine mediated apoptosis is stimulus specific in canine failed cardiomyocytes: a role for p38 MAPK, Fas‐L and cyclin D₁

Cited by 43 publications

References 19 publications

Transforming Growth Factor‐β Receptor III is a Potential Regulator of Ischemia‐Induced Cardiomyocyte Apoptosis

Transforming Growth Factor‐β Receptor III is a Potential Regulator of Ischemia‐Induced Cardiomyocyte Apoptosis

Role of 14-3-3-Mediated p38 Mitogen-Activated Protein Kinase Inhibition in Cardiac Myocyte Survival

Role of p38 inhibition in cardiac ischemia/reperfusion injury

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Hypoxia, angiotensin‐II, and norepinephrine mediated apoptosis is stimulus specific in canine failed cardiomyocytes: a role for p38 MAPK, Fas‐L and cyclin D1

Cited by 43 publications

References 19 publications

Transforming Growth Factor‐β Receptor III is a Potential Regulator of Ischemia‐Induced Cardiomyocyte Apoptosis

Transforming Growth Factor‐β Receptor III is a Potential Regulator of Ischemia‐Induced Cardiomyocyte Apoptosis

Role of 14-3-3-Mediated p38 Mitogen-Activated Protein Kinase Inhibition in Cardiac Myocyte Survival

Role of p38 inhibition in cardiac ischemia/reperfusion injury

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Hypoxia, angiotensin‐II, and norepinephrine mediated apoptosis is stimulus specific in canine failed cardiomyocytes: a role for p38 MAPK, Fas‐L and cyclin D₁