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This Article Full Text Full Text (PDF) All Versions of this Article: 295/2/H699    most recent 01204.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Google Scholar Articles by Huang, Y. Articles by O'Connell, T. D. PubMed PubMed Citation Articles by Huang, Y. Articles by O'Connell, T. D.

GATA4 is a survival factor in adult cardiac myocytes but is not required for 1A-adrenergic receptor survival signaling

Cardiovascular Research Center at Sanford Research/University of South Dakota and Department of Internal Medicine at The University of South Dakota School of Medicine, Sioux Falls, South Dakota

Submitted 17 October 2007 ; accepted in final form 3 June 2008

Recently, we defined an 1A-adrenergic receptor-ERK (1A-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 1-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 1A-ERK survival signaling in adult cardiac myocytes. We measured norepinephrine (NE)-induced cell death in cultured cardiac myocytes lacking 1-ARs (cultured from 1A/B-AR double-knockout mice, 1ABKO 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 1ABKO cardiac myocytes from NE-induced cell death. However, we found that the 1A-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 1A-survival signaling. In 1B-knockout cardiac myocytes, which express only the 1A-subtype and are protected from NE-induced cell death, GATA4 knockdown did not reverse 1A-survival signaling in response to NE. In summary, we found that GATA4 acted as a survival factor by preventing cell death in 1ABKO cardiac myocytes, but GATA4 was not activated by 1-AR stimulation and was not required for 1A-survival signaling in adult cardiac myocytes. This also identifies an important mechanistic difference in 1-signaling between adult and neonatal cardiac myocytes.

alpha-1-adrenergic receptors; extracellular signal regulated kinase; norepinephrine

This article has been cited by other articles:

				C. D. Wright, Q. Chen, N. L. Baye, Y. Huang, C. L. Healy, S. Kasinathan, and T. D. O'Connell Nuclear {alpha}1-Adrenergic Receptors Signal Activated ERK Localization to Caveolae in Adult Cardiac Myocytes Circ. Res., October 24, 2008; 103(9): 992 - 1000. [Abstract] [Full Text] [PDF]