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Citations to this article

Signals through gp130 upregulate bcl-x gene expression via STAT1-binding cis-element in cardiac myocytes.
Y Fujio, … , K Yamauchi-Takihara, T Kishimoto
Y Fujio, … , K Yamauchi-Takihara, T Kishimoto
Published June 15, 1997
Citation Information: J Clin Invest. 1997;99(12):2898-2905. https://doi.org/10.1172/JCI119484.
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Signals through gp130 upregulate bcl-x gene expression via STAT1-binding cis-element in cardiac myocytes.

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Abstract

We described recently the activation of the Janus kinasesignal transducer and activator of transcription (JakSTAT) and mitogen-activated protein (MAP) kinase pathways by leukemia inhibitory factor (LIF) through gp130, a signal transducer of IL-6-related cytokines, that transduces hypertrophic signals in cardiac myocytes. In addition, stimulation of gp130 by IL-6-related cytokines is known to exert a cytoprotective effect. In the present study, we investigated the possibility that activation of gp130 initiates activation of the cytoprotective genes in cardiac myocytes. Incubation of cardiac myocytes with LIF induced the expression of bcl-x, and the isoform that was induced by LIF was identified as bcl-xL. Induction of bcl-xL protein was also identified by Western blotting. Antisense oligonucleotide against bcl-x mRNA inhibited protective effect of LIF accompanied with the reduction in bclxL protein. We constructed bcl-x promoter-luciferase reporter gene plasmids (-639/+10- or -161/+10-luciferase), and transfected them to cardiac myocytes. LIF stimulation increased the luciferase activity of -639/+10-luciferase plasmids. Although -161/+10-luciferase plasmids presented comparable responsiveness to LIF, the basal transcription level was impaired. The LIF-responsive cis-element was localized to a DNA fragment (positions -161 to +10) that contains an interferon-gamma activation site (GAS) motif (GGA) at position -41 of the bcl-x gene promoter. This motif bound to STAT1, not to STAT3, and site-directed mutagenesis revealed that this motif was essential for LIF-responsive promoter activity. These data suggest that LIF induces bcl-x mRNA via STAT1 binding cis-element in cardiac myocytes, presenting cytoprotective effect.

Authors

Y Fujio, K Kunisada, H Hirota, K Yamauchi-Takihara, T Kishimoto

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Journal of Experimental Medicine 2000
Isolation and characterization of the murine cardiotrophin-1 gene: expression and norepinephrine-induced transcriptional activation
M Funamoto, S Hishinuma, Y Fujio, Y Matsuda, K Kunisada, H Oh, S Negoro, E Tone, T Kishimoto, K Yamauchi-Takihara
Journal of Molecular and Cellular Cardiology 2000
Rheumatoid arthritis synovial stromal cells inhibit apoptosis and up-regulate Bcl-xL expression by B cells in a CD49/CD29-CD106-dependent mechanism
K Hayashida, Y Shimaoka, T Ochi, PE Lipsky
Journal of immunology (Baltimore, Md. : 1950) 2000
Cardiotrophin-1 phosphorylates akt and BAD, and prolongs cell survival via a PI3K-dependent pathway in cardiac myocytes
K Kuwahara, Y Saito, I Kishimoto, Y Miyamoto, M Harada, E Ogawa, I Hamanaka, N Kajiyama, N Takahashi, T Izumi, R Kawakami, K Nakao
Journal of Molecular and Cellular Cardiology 2000
La vía JAK-STAT de señalización intracelular y su repercusión en oncogénesis, inmunomodulación y desarrollo
RF Duarte, DA Frank
Medicina Clínica 2000
Requirement of Activation of the Extracellular Signal-regulated Kinase Cascade in Myocardial Cell Hypertrophy
T Ueyama, S Kawashima, T Sakoda, Y Rikitake, T Ishida, M Kawai, T Yamashita, S Ishido, H Hotta, M Yokoyama
Journal of Molecular and Cellular Cardiology 2000
Akt Promotes Survival of Cardiomyocytes In Vitro and Protects Against Ischemia-Reperfusion Injury in Mouse Heart
Y Fujio, T Nguyen, D Wencker, RN Kitsis, K Walsh
Circulation 2000
Ischemia-induced STAT-1 Expression and Activation Play a Critical Role in Cardiomyocyte Apoptosis
A Stephanou, BK Brar, TM Scarabelli, AK Jonassen, DM Yellon, MS Marber, RA Knight, DS Latchman
The Journal of biological chemistry 2000
DNA Binding Specificity of Different STAT Proteins: COMPARISON OF IN VITRO SPECIFICITY WITH NATURAL TARGET SITES
GB Ehret, P Reichenbach, U Schindler, CM Horvath, S Fritz, M Nabholz, P Bucher
The Journal of biological chemistry 2000
Effects of Protease Inhibitors and Antioxidants on In Vitro Survival of Porcine Primordial Germ Cells1
CK Lee, RL Weaks, GA Johnson, FW Bazer, JA Piedrahita
Biology of reproduction 2000
Control of myeloid differentiation and survival by Stats
TE Smithgall, SD Briggs, S Schreiner, EC Lerner, H Cheng, MB Wilson
Oncogene 2000
Cooperation between STAT5 and phosphatidylinositol 3-kinase in the IL-3-dependent survival of a bone marrow derived cell line
SC Santos, S Dumon, P Mayeux, S Gisselbrecht, F Gouilleux
Oncogene 2000
Signal Transducer and Activator of Transcription 3 Is Required for Glycoprotein 130-mediated Induction of Vascular Endothelial Growth Factor in Cardiac Myocytes
M Funamoto, Y Fujio, K Kunisada, S Negoro, E Tone, T Osugi, H Hirota, M Izumi, K Yoshizaki, K Walsh, T Kishimoto, K Yamauchi-Takihara
The Journal of biological chemistry 2000
From Molecule to Men
M Zehender, H Just, G Breithardt
2000
Apoptosis in Cardiac Biology
H Schunkert, GA Riegger
2000
The Hypertrophied Heart
N Takeda, M Nagano, NS Dhalla
2000
Leukemia-Inhibitory Factor—Neuroimmune Modulator of Endocrine Function*
CJ Auernhammer, S Melmed
Endocrine reviews 2000
The Rel/NF-κB Family Directly Activates Expression of the Apoptosis Inhibitor Bcl-x L
C Chen, LC Edelstein, C Gélinas
Molecular and cellular biology 2000
Decrease Tyrosine Phosphorylation of Stat3 in Human Myocardium with End-Stage Congestive Heart Failure
C Wei, JS McLaughlin
Microscopy and Microanalysis 2000
Ectopic expression of fibroblast growth factor receptor 3 promotes myeloma cell proliferation and prevents apoptosis
EE Plowright, Z Li, PL Bergsagel, M Chesi, DL Barber, DR Branch, RG Hawley, AK Stewart
Blood 2000
Akt promotes survival of cardiomyocytes in vitro and protects against ischemia-reperfusion injury in mouse heart.
Fujio Y, Nguyen T, Wencker D, Kitsis RN, Walsh K
Circulation 2000
STAT signaling in the pathogenesis and treatment of cancer
DA Frank
Molecular Medicine 1999
Extracellular matrix regulates apoptosis in mammary epithelium through a control on insulin signaling
N Farrelly, YJ Lee, J Oliver, C Dive, CH Streuli
The Journal of Cell Biology 1999
Regulation of apoptosis in myeloid cells by interferon consensus sequence-binding protein
L Gabriele, J Phung, J Fukumoto, D Segal, IM Wang, P Giannakakou, NA Giese, K Ozato, HC 3rd
Journal of Experimental Medicine 1999
Is apoptosis an important pathogenic factor in cardiovascular disease?
Aukrust, Gullestad, Froland
European Journal of Clinical Investigation 1999
Constitutive Activation of Stat3 Signaling Confers Resistance to Apoptosis in Human U266 Myeloma Cells
R Catlett-Falcone, TH Landowski, MM Oshiro, J Turkson, A Levitzki, R Savino, G Ciliberto, L Moscinski, JL Fernández-Luna, G Nuñez, WS Dalton, R Jove
Immunity 1999
Signalling through the JAK–STAT pathway in the developing brain
E Cattaneo, L Conti, C De-Fraja
Trends in Neurosciences 1999
Fetal Anemia and Apoptosis of Red Cell Progenitors in Stat5a−/−5b−/− Mice
M Socolovsky, AE Fallon, S Wang, C Brugnara, HF Lodish
Cell 1999
Regulation of Apoptosis in Myeloid Cells by Interferon Consensus Sequence-Binding Protein
L Gabriele, J Phung, J Fukumoto, D Segal, IM Wang, P Giannakakou, NA Giese, K Ozato, HC Morse
Journal of Experimental Medicine 1999
The mitochondrial apoptotic pathway is activated by serum and glucose deprivation in cardiac myocytes
S Bialik, VL Cryns, A Drincic, S Miyata, AL Wollowick, A Srinivasan, RN Kitsis
Circulation research 1999
Cardiac myocytes produce interleukin-6 in culture and in viable border zone of reperfused infarctions
M Gwechenberger, LH Mendoza, KA Youker, NG Frangogiannis, CW Smith, LH Michael, ML Entman
Circulation 1999
IL-3 dependent regulation of Bcl-xL gene expression by STAT5 in a bone marrow derived cell line
S Dumon, SC Santos, F Debierre-Grockiego, V Gouilleux-Gruart, L Cocault, C Boucheron, P Mollat, S Gisselbrecht, F Gouilleux
Oncogene 1999
Erythropoietin Can Induce the Expression of Bcl-x L through Stat5 in Erythropoietin-dependent Progenitor Cell Lines
M Silva, A Benito, C Sanz, F Prosper, D Ekhterae, G Nuñez, JL Fernandez-Luna
The Journal of biological chemistry 1999
Mast Cells Cause Apoptosis of Cardiomyocytes and Proliferation of Other Intramyocardial Cells In Vitro
M Hara, A Matsumori, K Ono, H Kido, MW Hwang, T Miyamoto, A Iwasaki, M Okada, K Nakatani, S Sasayama
Circulation 1999
Characterization of Insulin-Like Growth Factor-1–Induced Activation of the JAK/STAT Pathway in Rat Cardiomyocytes
T Takahashi, K Fukuda, J Pan, H Kodama, M Sano, S Makino, T Kato, T Manabe, S Ogawa
Circulation research 1999
Inhibition of Bcl-xL expression sensitizes normal human keratinocytes and epithelial cells to apoptotic stimuli
JK Taylor, QQ Zhang, BP Monia, EG Marcusson, NM Dean
Oncogene 1999
Interleukin-6-type cytokine signalling through the gp130/Jak/STAT pathway
PC Heinrich, I Behrmann, G Müller-Newen, F Schaper, L Graeve
Biochemical Journal 1998
STAT3 mediates the survival signal in oncogenicras-transfected intestinal epithelial cells
S Zushi, Y Shinomura, T Kiyohara, Y Miyazaki, S Kondo, M Sugimachi, Y Higashimoto, S Kanayama, Y Matsuzawa
International Journal of Cancer 1998
Generation of a novel stem cell factor-dependent mast cell progenitor
A Masuda, T Matsuguchi, K Yamaki, T Hayakawa, Y Yoshikai
Journal of immunology (Baltimore, Md. : 1950) 1998
Activation of Phosphatidylinositol 3-Kinase through Glycoprotein 130 Induces Protein Kinase B and p70 S6 Kinase Phosphorylation in Cardiac Myocytes
H Oh, Y Fujio, K Kunisada, H Hirota, H Matsui, T Kishimoto, K Yamauchi-Takihara
The Journal of biological chemistry 1998
Tyrosine 1101 of Tie2 Is the Major Site of Association of p85 and Is Required for Activation of Phosphatidylinositol 3-Kinase and Akt
CD Kontos, TP Stauffer, WP Yang, JD York, L Huang, MA Blanar, T Meyer, KG Peters
Molecular and cellular biology 1998

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