Rho/ROCK Pathway Contributes to the Activation of Extracellular Signal-regulated Kinase/GATA-4 during Myocardial Cell Hypertrophy

Q: What is the clinical evidence from this study?

Population: Myocardial cell hypertrophy. Intervention: Y-27632 and latrunculin B. Primary outcome: Phosphorylation of extracellular signal-regulated kinase 1/2 and DNA binding activity of cardiac GATA-4.

Tetsuhiko Yanazume; Koji Hasegawa; Hiromichi Wada; Tatsuya Morimoto; Mitsuru Abe; Teruhisa Kawamura; Shigetake Sasayama

doi:10.1074/jbc.m107924200

March 1, 2002Journal of Biological ChemistryOpen Access

Rho/ROCK Pathway Contributes to the Activation of Extracellular Signal-regulated Kinase/GATA-4 during Myocardial Cell Hypertrophy

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Key result

Inhibition of the Rho/ROCK pathway by Y-27632 suppressed phenylephrine-stimulated phosphorylation of ERK1/2 and increased the DNA binding activity of cardiac GATA-4.

Key Points

To determine whether the Rho/ROCK signaling pathway links to downstream extracellular signal-regulated kinase (ERK) and transcription factor GATA-4 activation during cardiac cell hypertrophy.
Cultured ventricular cardiac myocytes were stimulated with phenylephrine to trigger hypertrophic signaling cascades.
Transient transfection assays were performed using dominant-negative and constitutively active ROCK-I mutants to assess GATA-4-dependent endothelin-1 transcription.
Myocytes were treated with Y-27632 (a selective ROCK inhibitor) or latrunculin B (an actin polymerization inhibitor) to analyze ERK1/2 phosphorylation and GATA-4 DNA-binding activity.
Active ROCK-I stimulated GATA-4-dependent endothelin-1 transcription, whereas dominant-negative ROCK-I suppressed transcriptional activation.
Selective inhibition of ROCK with Y-27632 prevented phenylephrine-induced phosphorylation of ERK1/2 and reduced cardiac GATA-4 DNA-binding activity.
Inhibition of actin filament polymerization by latrunculin B blocked phenylephrine-stimulated ERK activation, GATA-4 binding, and cell enlargement.

Structured PICO

P

Population

Ventricular cardiac myocytes

I

Intervention

Modulation of Rho/ROCK pathway (transient transfection with ROCK-I mutants, Y-27632, latrunculin B)

C

Comparator

Untreated/control cells

O

Outcome

GATA-4-dependent endothelin-1 transcription and ERK1/2 phosphorylationsurrogate

The Rho/ROCK pathway is linked to downstream GATA-4 via the activation of extracellular signal-regulated kinases during myocardial cell hypertrophy, with actin dynamics providing a convergence point.

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Implication

Findings in animal models warrant caution before clinical translation; leaves open Rho/ROCK modulation of hypertrophy signaling.

Abstract

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Cite This Study

Yanazume et al. (2002) studied Myocardial cell hypertrophy. Y-27632 and latrunculin B was evaluated on Phosphorylation of extracellular signal-regulated kinase 1/2 and DNA binding activity of cardiac GATA-4. Inhibition of the Rho/ROCK pathway by Y-27632 suppressed phenylephrine-stimulated phosphorylation of ERK1/2 and increased the DNA binding activity of cardiac GATA-4.

synapsesocial.com/papers/6a20046b9d62e9997c04b479 https://doi.org/10.1074/jbc.m107924200

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Rho/ROCK Pathway Contributes to the Activation of Extracellular Signal-regulated Kinase/GATA-4 during Myocardial Cell Hypertrophy

Key Points

Structured PICO

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Implication

Abstract

Discussion

Cite This Study

Rho/ROCK Pathway Contributes to the Activation of Extracellular Signal-regulated Kinase/GATA-4 during Myocardial Cell Hypertrophy

Key Points

Structured PICO

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Implication

Abstract

Discussion

Cite This Study

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