GATA4 is a survival factor in adult cardiac myocytes but is not required for α1A-adrenergic receptor survival signaling

Yuan Huang, Casey D. Wright, Satoru Kobayashi, Chastity L. Healy, Megan Elgethun, Andrew Cypher, Qiangrong Liang, Timothy D. O'Connell

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Recently, we defined an α1A-adrenergic receptor-ERK (α1A-AR-ERK) survival signaling pathway in adult cardiac myocytes. Previous studies in neonatal cardiac myocytes indicated that the cardiac-specific transcription factor GATA4 is a downstream mediator of α1-ERK signaling and that phosphorylation of GATA4 by ERK increases DNA binding and transcriptional activity. Therefore, we examined GATA4 as a potential downstream effector of α1A-ERK survival signaling in adult cardiac myocytes. We measured norepinephrine (NE)-induced cell death in cultured cardiac myocytes lacking α1-ARs (cultured from α1A/B-AR double-knockout mice, α1ABKO mice) that are susceptible to cell death induced by several proapoptotic stimuli, including NE. Our results show that overexpression of GATA4 is sufficient to protect α1ABKO cardiac myocytes from NE-induced cell death. However, we found that the α1A-subtype did not induce phosphorylation or increase the activity of GATA4 in adult mouse cardiac myocytes in culture or in vivo. Furthermore, we examined the effect of siRNA-mediated knockdown of GATA4 on α1A-survival signaling. In α1B-knockout cardiac myocytes, which express only the α1A-subtype and are protected from NE-induced cell death, GATA4 knockdown did not reverse α1A-survival signaling in response to NE. In summary, we found that GATA4 acted as a survival factor by preventing cell death in α1ABKO cardiac myocytes, but GATA4 was not activated by α1-AR stimulation and was not required for α1A-survival signaling in adult cardiac myocytes. This also identifies an important mechanistic difference in α1-signaling between adult and neonatal cardiac myocytes.

Original languageEnglish (US)
Pages (from-to)H699-H707
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume295
Issue number2
DOIs
StatePublished - Aug 2008

Keywords

  • Alpha-1-adrenergic receptors
  • Extracellular signal regulated kinase
  • Norepinephrine

Fingerprint Dive into the research topics of 'GATA4 is a survival factor in adult cardiac myocytes but is not required for α1A-adrenergic receptor survival signaling'. Together they form a unique fingerprint.

  • Cite this