Distinct regulation of B-type natriuretic peptide transcription by p38 MAPK isoforms

Koivisto, Elina; Kaikkonen, Leena; Tokola, Heikki; Pikkarainen, Sampsa; Aro, Jani; Pennanen, Harri; Karvonen, Teemu; Rysä, Jaana; Kerkelä, Risto; Ruskoaho, Heikki

doi:10.1016/j.mce.2011.02.015

Cited by 30 publications

(27 citation statements)

References 48 publications

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“…Direct injections of adenoviruses expressing p38α or p38β into the left ventricular wall of adult rats demonstrated that p38α stimulates fibrosis-related factors whereas p38β attenuated the ET-1-induced expression of the B-type natriuretic peptide. These findings indicate that p38α participates in the regulation of fibrotic remodeling process, and p38β stimulates the agonist-induced activation of the B-type natriuretic peptide and, thereby, elicits inhibitory effects on growth factors (Koivisto et al, 2011). DN-p38α transgenic mice exhibited cardiac hypertrophy despite the reduced p38α activity (Braz et al, 2003, Zhang et al, 2003).…”

Section: Mapks In Chronic Cardiac Stress (Hypertrophy and Heart Famentioning

confidence: 94%

Crosstalk between mitogen-activated protein kinases and mitochondria in cardiac diseases: Therapeutic perspectives

Javadov

Jang

Agostini

2014

Pharmacology & Therapeutics

132

125

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Cardiovascular diseases cause more mortality and morbidity worldwide than any other diseases. Although many intracellular signaling pathways influence cardiac physiology and pathology, the mitogen-activated protein kinase (MAPK) family has garnered significant attention because of its vast implications in signaling and cross-talk with other signaling networks. The extensively studied MAPKs ERK1/2, p38, JNK, and ERK5, demonstrate unique intracellular signaling mechanisms, responding to a myriad of mitogens and stressors and influencing the signaling of cardiac development, metabolism, performance, and pathogenesis. Definitive relationships between MAPK signaling and cardiac dysfunction remain elusive, despite 30 years of extensive clinical studies and basic research of various animal/cell models, severities of stress, and types of stimuli. Still, several studies have proven the importance of MAPK cross-talk with mitochondria, powerhouses of the cell that provide over 80% of ATP for normal cardiomyocyte function and play a crucial role in cell death. Although many questions remain unanswered, there exists enough evidence to consider the possibility of targeting MAPK-mitochondria interactions in the prevention and treatment of heart disease. The goal of this review is to integrate previous studies into a discussion of MAPKs and MAPK-mitochondria signaling in cardiac diseases, such as myocardial infarction (ischemia), hypertrophy and heart failure. A comprehensive understanding of relevant molecular mechanisms, as well as challenges for studies in this area, will facilitate the development of new pharmacological agents and genetic manipulations for therapy of cardiovascular diseases.

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Section: Mapks In Chronic Cardiac Stress (Hypertrophy and Heart Famentioning

confidence: 94%

Crosstalk between mitogen-activated protein kinases and mitochondria in cardiac diseases: Therapeutic perspectives

Javadov

Jang

Agostini

2014

Pharmacology & Therapeutics

132

125

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“…The MKK3b, MKK6b and WT p38β adenoviruses have been described previously [20]. The ATF3–overexpressing adenovirus (serotype 5) was generated as previously described [21].…”

Section: Methodsmentioning

confidence: 99%

Characterization of the Regulatory Mechanisms of Activating Transcription Factor 3 by Hypertrophic Stimuli in Rat Cardiomyocytes

et al. 2014

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AimsActivating transcription factor 3 (ATF3) is a stress-activated immediate early gene suggested to have both detrimental and cardioprotective role in the heart. Here we studied the mechanisms of ATF3 activation by hypertrophic stimuli and ATF3 downstream targets in rat cardiomyocytes.Methods and ResultsWhen neonatal rat cardiomyocytes were exposed to endothelin-1 (ET-1, 100 nM) and mechanical stretching in vitro, maximal increase in ATF3 expression occurred at 1 hour. Inhibition of extracellular signal-regulated kinase (ERK) by PD98059 decreased ET-1– and stretch–induced increase of ATF3 protein but not ATF3 mRNA levels, whereas protein kinase A (PKA) inhibitor H89 attenuated both ATF3 mRNA transcription and protein expression in response to ET-1 and stretch. To characterize further the regulatory mechanisms upstream of ATF3, p38 mitogen-activated protein kinase (MAPK) signaling was investigated using a gain-of-function approach. Adenoviral overexpression of p38α, but not p38β, increased ATF3 mRNA and protein levels as well as DNA binding activity. To investigate the role of ATF3 in hypertrophic process, we overexpressed ATF3 by adenovirus-mediated gene transfer. In vitro, ATF3 gene delivery attenuated the mRNA transcription of interleukin-6 (IL-6) and plasminogen activator inhibitor-1 (PAI-1), and enhanced nuclear factor-κB (NF-κB) and Nkx-2.5 DNA binding activities. Reduced PAI-1 expression was also detected in vivo in adult rat heart by direct intramyocardial adenovirus-mediated ATF3 gene delivery.ConclusionsThese data demonstrate that ATF3 activation by ET-1 and mechanical stretch is partly mediated through ERK and cAMP-PKA pathways, whereas p38 MAPK pathway is involved in ATF3 activation exclusively through p38α isoform. ATF3 activation caused induction of modulators of the inflammatory response NF-κB and Nkx-2.5, as well as attenuation of pro-fibrotic and pro-inflammatory proteins IL-6 and PAI-1, suggesting cardioprotective role for ATF3 in the heart.

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“…GATA4 is phosphorylated at Ser105 by both ERK and p38,21, 22, 23 regulating its DNA‐binding activity and transcriptional activity 22, 23, 24, 25, 26. In addition to GATA4, a number of other transcriptional regulators, such as nuclear factor of activated T‐cells (NFAT), NKX‐2.5, Elk‐1, activator protein 1, myocardin, serum response factor, and nuclear factor kappa B, have been shown to participate in transcriptional regulation of BNP 20, 27, 28, 29, 30, 31, 32. Several studies have also indicated a central role for M‐CAT element, a thyroid‐responsive element and shear stress‐responsive element on the BNP promoter regulating BNP transcriptional activity 33, 34, 35, 36.…”

Section: Regulation Of Anp and Bnp Gene Expressionmentioning

confidence: 99%

Natriuretic Peptides in the Regulation of Cardiovascular Physiology and Metabolic Events

Kerkelä

Ulvila

Magga

2015

JAHA

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131

108

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Distinct regulation of B-type natriuretic peptide transcription by p38 MAPK isoforms

Cited by 30 publications

References 48 publications

Crosstalk between mitogen-activated protein kinases and mitochondria in cardiac diseases: Therapeutic perspectives

Crosstalk between mitogen-activated protein kinases and mitochondria in cardiac diseases: Therapeutic perspectives

Characterization of the Regulatory Mechanisms of Activating Transcription Factor 3 by Hypertrophic Stimuli in Rat Cardiomyocytes

Natriuretic Peptides in the Regulation of Cardiovascular Physiology and Metabolic Events

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