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STAT3 Activation in Pressure-Overloaded Feline Myocardium: Role for Integrins and the Tyrosine Kinase BMX

Growth, survival and cytoskeletal rearrangement of cardiomyocytes are critical for cardiac hypertrophy. Signal transducer and activator of transcription-3 (STAT3) activation is an important cardioprotective factor associated with cardiac hypertrophy. Although STAT3 activation has been reported via s...

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Autores principales: Willey, Christopher D., Palanisamy, Arun P., Johnston, Rebecca K., Mani, Santhosh K., Shiraishi, Hirokazu, Tuxworth, William J., Zile, Michael R., Balasubramanian, Sundaravadivel, Kuppuswamy, Dhandapani
Formato: Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2008
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2443357/
https://www.ncbi.nlm.nih.gov/pubmed/18612371
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author Willey, Christopher D.
Palanisamy, Arun P.
Johnston, Rebecca K.
Mani, Santhosh K.
Shiraishi, Hirokazu
Tuxworth, William J.
Zile, Michael R.
Balasubramanian, Sundaravadivel
Kuppuswamy, Dhandapani
author_facet Willey, Christopher D.
Palanisamy, Arun P.
Johnston, Rebecca K.
Mani, Santhosh K.
Shiraishi, Hirokazu
Tuxworth, William J.
Zile, Michael R.
Balasubramanian, Sundaravadivel
Kuppuswamy, Dhandapani
author_sort Willey, Christopher D.
collection PubMed
description Growth, survival and cytoskeletal rearrangement of cardiomyocytes are critical for cardiac hypertrophy. Signal transducer and activator of transcription-3 (STAT3) activation is an important cardioprotective factor associated with cardiac hypertrophy. Although STAT3 activation has been reported via signaling through Janus Kinase 2 (JAK2) in several cardiac models of hypertrophy, the importance of other nonreceptor tyrosine kinases (NTKs) has not been explored. Utilizing an in vivo feline right ventricular pressure-overload (RVPO) model of hypertrophy, we demonstrate that in 48 h pressure-overload (PO) myocardium, STAT3 becomes phosphorylated and redistributed to detergent-insoluble fractions with no accompanying JAK2 activation. PO also caused increased levels of phosphorylated STAT3 in both cytoplasmic and nuclear fractions. To investigate the role of other NTKs, we used our established in vitro cell culture model of hypertrophy where adult feline cardiomyocytes are embedded three-dimensionally (3D) in type-I collagen and stimulated with an integrin binding peptide containing an Arg-Gly-Asp (RGD) motif that we have previously shown to recapitulate the focal adhesion complex (FAC) formation of 48 h RVPO. RGD stimulation of adult cardiomyocytes in vitro caused both STAT3 redistribution and activation that were accompanied by the activation and redistribution of c-Src and the TEC family kinase, BMX, but not JAK2. However, infection with dominant negative c-Src adenovirus was unable to block RGD-stimulated changes on either STAT3 or BMX. Further analysis in vivo in 48 h PO myocardium showed the presence of both STAT3 and BMX in the detergent-insoluble fraction with their complex formation and phosphorylation. Therefore, these studies indicate a novel mechanism of BMX-mediated STAT3 activation within a PO model of cardiac hypertrophy that might contribute to cardiomyocyte growth and survival.
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spelling pubmed-24433572008-07-08 STAT3 Activation in Pressure-Overloaded Feline Myocardium: Role for Integrins and the Tyrosine Kinase BMX Willey, Christopher D. Palanisamy, Arun P. Johnston, Rebecca K. Mani, Santhosh K. Shiraishi, Hirokazu Tuxworth, William J. Zile, Michael R. Balasubramanian, Sundaravadivel Kuppuswamy, Dhandapani Int J Biol Sci Research Paper Growth, survival and cytoskeletal rearrangement of cardiomyocytes are critical for cardiac hypertrophy. Signal transducer and activator of transcription-3 (STAT3) activation is an important cardioprotective factor associated with cardiac hypertrophy. Although STAT3 activation has been reported via signaling through Janus Kinase 2 (JAK2) in several cardiac models of hypertrophy, the importance of other nonreceptor tyrosine kinases (NTKs) has not been explored. Utilizing an in vivo feline right ventricular pressure-overload (RVPO) model of hypertrophy, we demonstrate that in 48 h pressure-overload (PO) myocardium, STAT3 becomes phosphorylated and redistributed to detergent-insoluble fractions with no accompanying JAK2 activation. PO also caused increased levels of phosphorylated STAT3 in both cytoplasmic and nuclear fractions. To investigate the role of other NTKs, we used our established in vitro cell culture model of hypertrophy where adult feline cardiomyocytes are embedded three-dimensionally (3D) in type-I collagen and stimulated with an integrin binding peptide containing an Arg-Gly-Asp (RGD) motif that we have previously shown to recapitulate the focal adhesion complex (FAC) formation of 48 h RVPO. RGD stimulation of adult cardiomyocytes in vitro caused both STAT3 redistribution and activation that were accompanied by the activation and redistribution of c-Src and the TEC family kinase, BMX, but not JAK2. However, infection with dominant negative c-Src adenovirus was unable to block RGD-stimulated changes on either STAT3 or BMX. Further analysis in vivo in 48 h PO myocardium showed the presence of both STAT3 and BMX in the detergent-insoluble fraction with their complex formation and phosphorylation. Therefore, these studies indicate a novel mechanism of BMX-mediated STAT3 activation within a PO model of cardiac hypertrophy that might contribute to cardiomyocyte growth and survival. Ivyspring International Publisher 2008-06-27 /pmc/articles/PMC2443357/ /pubmed/18612371 Text en © Ivyspring International Publisher. This is an open-access article distributed under the terms of the Creative Commons License (http://creativecommons.org/licenses/by-nc-nd/3.0/). Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited.
spellingShingle Research Paper
Willey, Christopher D.
Palanisamy, Arun P.
Johnston, Rebecca K.
Mani, Santhosh K.
Shiraishi, Hirokazu
Tuxworth, William J.
Zile, Michael R.
Balasubramanian, Sundaravadivel
Kuppuswamy, Dhandapani
STAT3 Activation in Pressure-Overloaded Feline Myocardium: Role for Integrins and the Tyrosine Kinase BMX
title STAT3 Activation in Pressure-Overloaded Feline Myocardium: Role for Integrins and the Tyrosine Kinase BMX
title_full STAT3 Activation in Pressure-Overloaded Feline Myocardium: Role for Integrins and the Tyrosine Kinase BMX
title_fullStr STAT3 Activation in Pressure-Overloaded Feline Myocardium: Role for Integrins and the Tyrosine Kinase BMX
title_full_unstemmed STAT3 Activation in Pressure-Overloaded Feline Myocardium: Role for Integrins and the Tyrosine Kinase BMX
title_short STAT3 Activation in Pressure-Overloaded Feline Myocardium: Role for Integrins and the Tyrosine Kinase BMX
title_sort stat3 activation in pressure-overloaded feline myocardium: role for integrins and the tyrosine kinase bmx
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2443357/
https://www.ncbi.nlm.nih.gov/pubmed/18612371
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