Transcription factor GATA-4 is involved in erythropoietin-induced cardioprotection against myocardial ischemia/reperfusion injury

Shan, Xiaohong; Xu, Xuan; Cao, Bin; Wang, Yongmei; Guo, Lin; Zhu, Quan; Li, Jing; Que, Linli; Chen, Qi; Ha, Tuanzhu; Li, Chuanfu; Li, Yuehua

doi:10.1016/j.ijcard.2008.03.043

Cited by 24 publications

(31 citation statements)

References 38 publications

(59 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…21) Additionally, GATA4 has been demonstrated to regulate the expression of Bcl-2, an anti-apoptotic protein, in cardiac myocytes, and has been shown to be involved in erythropoietin-induced cardioprotection against ischemia/reperfusion injury in the mouse heart. 22,23) Regulation of GATA4 activity by post-translational modification and protein interaction GATA4 expression and post-translational modifications are altered in the heart during cardiac hypertrophy and heart failure. GATA4 post-transcriptional modifications are important for transcriptional activity, and GATA4 activity is reportedly regulated by modifications such as acetylation, phosphorylation, methylation, and SUMOylation (Table).…”

Section: Gata4mentioning

confidence: 99%

Regulation of Cardiac Transcription Factor GATA4 by Post-Translational Modification in Cardiomyocyte Hypertrophy and Heart Failure

et al. 2016

View full text Add to dashboard Cite

SummaryHeart failure is a leading cause of cardiovascular mortality in industrialized countries. During development and deterioration of heart failure, cardiomyocytes undergo maladaptive hypertrophy, and changes in the cellular phenotype are accompanied by reinduction of the fetal gene program. Gene expression in cardiomyocytes is regulated by various nuclear transcription factors, co-activators, and co-repressors. The zinc finger protein GATA4 is one such transcription factor involved in the regulation of cardiomyocyte hypertrophy. In response to hypertrophic stimuli such as those involving the sympathetic nervous and renin-angiotensin systems, changes in protein interaction and/or post-translational modifications of GATA4 cause hypertrophic gene transcription in cardiomyocytes. In this article, we focus on cardiac nuclear signaling molecules, especially GATA4, that are promising as potential targets for heart failure therapy. (Int Heart J 2016; 57: 672-675)

show abstract

Section: Gata4mentioning

confidence: 99%

Regulation of Cardiac Transcription Factor GATA4 by Post-Translational Modification in Cardiomyocyte Hypertrophy and Heart Failure

et al. 2016

View full text Add to dashboard Cite

show abstract

“…6) In previous studies, EPO was shown to convey a cardioprotective effect against the regulation of GATA-4 protein level via various signaling pathways including the PI3K/AKT and ERK signaling pathways. 22,34) EPO increased GATA-4 phosphorylation and enhanced the transcriptional activation of GATA-4 after I/R injury. 22) Phosphorylation is a form of post-translational modification that plays an important role in the functional performance of GATA-4 in physiological as well as pathological cellular processes.…”

Section: Discussionmentioning

confidence: 88%

“…22,34) EPO increased GATA-4 phosphorylation and enhanced the transcriptional activation of GATA-4 after I/R injury. 22) Phosphorylation is a form of post-translational modification that plays an important role in the functional performance of GATA-4 in physiological as well as pathological cellular processes. 11) In a previous study performed under normoxic conditions, we observed that EPO-induced phosphorylation of GATA-4 serine-261 lead to enhanced acetylation, but not ubiquitination, of GATA-4.…”

Section: Discussionmentioning

confidence: 88%

“…33) Considering the clinical prevalence and significance of myocardial infarction, GATA-4 activation has been proposed as an important component of the transcriptional response to hypoxia. 22) Indeed, GATA-4 could decrease the rate of apoptosis at an early time point and enhance angiogenesis in the infarcted myocardium. 33) Although EPO is a principle regulator of erythropoiesis, EPO receptors are also expressed by other cell types, and EPO has been shown to protect the myocardium against I/R injury or hypoxia 3) via various signal transduction pathways.…”

Section: Discussionmentioning

confidence: 99%

“…22) Unlike I/R injury, however, the influence of EPO on GATA-4 activity under hypoxic conditions without reperfusion has not been elucidated, while the protective role of EPO or GATA-4 on hypoxia-induced cardiomyocyte apoptosis and infarction has been demonstrated separately. 22,23) In this study, we investigated the influence of the EPO-ERK signaling pathway on GATA-4 stability in terms of post-translational modifications including the culprit amino acid residue under hypoxic conditions without reperfusion.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Erythropoietin Prevents Hypoxia-Induced GATA-4 Ubiquitination <i>via</i> Phosphorylation of Serine 105 of GATA-4

Jun

Shin

Kim

et al. 2013

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

Erythropoietin (EPO), an essential hormone for erythropoiesis, can provide protection against myocardial ischemia/reperfusion (I/R) injury and hypoxic apoptosis. GATA-4 is a zinc finger transcription factor, and its activation and post-translational modification are essential components in the transcriptional response to hypoxia. GATA-4 has also been reported to play a role in the cellular mechanisms of EPO-induced myocardial protection against I/R injury. In this study, we aimed to investigate the influence of EPO on GATA-4 protein stability and post-translational modification under hypoxic conditions without reperfusion. EPO induced cell viability under long-term hypoxia. EPO significantly increased phosphorylation of GATA-4 via the extracellular signal-regulated kinase (ERK) signaling pathway and reduced hypoxia-induced GATA-4 ubiquitination, which enhanced GATA-4 stability under hypoxia. ERK activation by over-expression of constitutively active mitogen-activated protein kinase 1 (MEK1) strongly increased GATA-4 phosphorylation and its protein levels and decreased GATA-4 ubiquitination under hypoxia. Despite ERK activation, GATA-4 ubiquitination was not affected under hypoxia in a GATA-4-S105A mutant. Under hypoxic condition without reperfusion, EPO-induced ERK activation was associated with post-translational modification of GATA-4, mediated by enhancement of phosphorylation of GATA-4 at Ser-105. Subsequent attenuation of GATA-4 ubiquitination led to increases in GATA-4 protein stability, which resulted in increased cell viability under hypoxia.

show abstract

Erythropoietin‐activated ERK/MAP kinase enhances GATA‐4 acetylation via phosphorylation of serine 261 of GATA‐4

Jun

Shim

Ryoo

et al. 2012

Journal Cellular Physiology

View full text Add to dashboard Cite

GATA-4, a zinc finger transcription factor, plays a critical role in heart development. Previous studies have shown that p300-targeted GATA-4 acetylation increases GATA-4 stability and transcriptional activity, which then stimulates hypertrophy of cardiomyocyte. Erythropoietin (EPO), an essential hypoxia-induced hormone for normal erythropoiesis, is known to exert cardioprotective effects against heart disease of either ischemic or non-ischemic origins. Although, various action mechanisms of EPO have been proposed in the diseased heart, its action mechanism in normal condition has not been investigated. In this study, we aimed to investigate the influence of EPO-induced ERK signaling on the regulation of GATA-4 protein action. EPO treatment increased the protein level of endogenous GATA-4 via ERK signaling pathway. Inhibition of ERK activity by U0126, suppressed EPO-induced expression of GATA-4 protein in rat cardiac myocytes. In addition, ERK activation by over-expression of constitutively active MEK1 strongly increased GATA-4 phosphorylation and subsequently enhanced its acetylation in P19 cells. EPO-induced ERK activation further increased the association of GATA-4 with p300. On the other hand, knock-down of p300 using siRNA diminished ERK-induced GATA-4 acetylation. As EPO-induced GATA-4 phosphorylation via ERK signaling pathway directly correlated with GATA-4 acetylation, we investigated to identify the ERK-dependent phosphorylation sites in GATA-4. Site-directed mutagenesis implicated that Ser-261 in GATA-4 played an important role for ERK-mediated GATA-4 acetylation. Taken together, these results indicated that EPO-induced ERK signaling activation increased GATA-4 phosphorylation and acetylation, partly via increase in the association between GATA-4 and p300, and these processes required the phosphorylation of GATA-4 at Ser-261 residue.

show abstract

Transcription factor GATA-4 is involved in erythropoietin-induced cardioprotection against myocardial ischemia/reperfusion injury

Cited by 24 publications

References 38 publications

Regulation of Cardiac Transcription Factor GATA4 by Post-Translational Modification in Cardiomyocyte Hypertrophy and Heart Failure

Regulation of Cardiac Transcription Factor GATA4 by Post-Translational Modification in Cardiomyocyte Hypertrophy and Heart Failure

Erythropoietin Prevents Hypoxia-Induced GATA-4 Ubiquitination <i>via</i> Phosphorylation of Serine 105 of GATA-4

Erythropoietin‐activated ERK/MAP kinase enhances GATA‐4 acetylation via phosphorylation of serine 261 of GATA‐4

Contact Info

Product

Resources

About