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May 28, 2004Journal of Biological ChemistryOpen Access

Mitogen-activated Protein Kinases p38 and ERK 1/2 Mediate the Wall Stress-induced Activation of GATA-4 Binding in Adult Heart

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Population

Isolated perfused rat hearts and isolated rat atria

Comparison

Increased left ventricular wall stress with or… vs Baseline or stretch without inhibitors

Design

Preclinical

Authors

OTOlli TenhunenOulu University HospitalBSBalázs SármánUzsoki HospitalRKRisto KerkeläHeart Failure / Cardiomyopathy

Discussion

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Implication

p38/ERK pathways mediate stretch-induced GATA-4 activation in adult rat hearts; extends in vitro data but leaves open human hypertrophic relevance.

Structured PICO

P
Population
Isolated perfused rat hearts and isolated rat atria
I
Intervention
Increased left ventricular wall stress (via balloon inflation) with or without MAPK inhibitors (SB239063 for p38, U0126 for MEK1/2, CEP11004 for JNK)
C
Comparator
Baseline (no stretch) or stretch without inhibitors
O
Outcome
GATA-4 DNA binding activity and levels of phosphorylated p38 kinase, extracellular signal-regulated protein kinase (ERK), and c-Jun N-terminal protein kinase (JNK)surrogate

Both p38 and ERK 1/2 are required for stretch-induced GATA-4 binding in the intact adult rat heart, highlighting their role in the cardiac hypertrophic response.

Cite This Study

Tenhunen et al. (2004) studied this question.

synapsesocial.com/papers/6a83a65720cfb2932ffe1850https://doi.org/10.1074/jbc.m314317200
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1GATA4 Mediates Activation of the B-Type Natriuretic Peptide Gene Expression in Response to Hemodynamic Stress2001 · 53 citations
  2. 2GATA-4 Is a Nuclear Mediator of Mechanical Stretch-activated Hypertrophic Program2003 · 123 citations
  3. 3Regulation of Cardiomyocyte Mechanotransduction by the Cardiac Cycle2001 · 62 citations
  4. 4The MEKK1-JNK pathway plays a protective role in pressure overload but does not mediate cardiac hypertrophy2002 · 168 citations
  5. 5Localization and regulation of c-fos and c-jun protooncogene induction by systolic wall stress in normal and hypertrophied rat hearts.1991 · 107 citations