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. 2001 Oct 15;359(Pt 2):375–380. doi: 10.1042/0264-6021:3590375

Endothelin-1 induces phosphorylation of GATA-4 transcription factor in the HL-1 atrial-muscle cell line.

K Kitta 1, S A Clément 1, J Remeika 1, J B Blumberg 1, Y J Suzuki 1
PMCID: PMC1222156  PMID: 11583584

Abstract

The transcription factor GATA-4 plays a central role in the regulation of cardiac-muscle gene transcription. The present study demonstrates that endothelin-1 (ET-1) induces GATA-4 activation and phosphorylation. The treatment of HL-1 adult mouse atrial-muscle cells with ET-1 (30 nM) caused a rapid increase in the DNA binding activity of GATA-4 within 3 min. The activation was associated with an upward mobility shift of the GATA-4 band on native PAGE in an electrophoretic- mobility-shift assay. The upward shift of the GATA-4 band also occurred on SDS/PAGE as monitored by immunoblotting. The in vitro treatment of nuclear extracts with lambda-protein phosphatase abolished the upward shift, indicating that GATA-4 was phosphorylated. ET-1 activated the p44/42 mitogen-activated protein kinase (MAPK) and the MAPK kinase (MEK) within 3 min, and PD98059 (a specific inhibitor of MEK) abolished the ET-1-induced GATA-4 phosphorylation. PMA also caused the rapid activation of MAPK and the phosphorylation of GATA-4. In contrast, the activation of MAPK by phenylephrine or H(2)O(2) was weak and did not lead to GATA-4 phosphorylation. Thus ET-1 induces a GATA-4 phosphorylation by activating a MEK-MAPK pathway.

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Selected References

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  1. Alessi D. R., Cuenda A., Cohen P., Dudley D. T., Saltiel A. R. PD 098059 is a specific inhibitor of the activation of mitogen-activated protein kinase kinase in vitro and in vivo. J Biol Chem. 1995 Nov 17;270(46):27489–27494. doi: 10.1074/jbc.270.46.27489. [DOI] [PubMed] [Google Scholar]
  2. Arceci R. J., King A. A., Simon M. C., Orkin S. H., Wilson D. B. Mouse GATA-4: a retinoic acid-inducible GATA-binding transcription factor expressed in endodermally derived tissues and heart. Mol Cell Biol. 1993 Apr;13(4):2235–2246. doi: 10.1128/mcb.13.4.2235. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bogoyevitch M. A., Glennon P. E., Andersson M. B., Clerk A., Lazou A., Marshall C. J., Parker P. J., Sugden P. H. Endothelin-1 and fibroblast growth factors stimulate the mitogen-activated protein kinase signaling cascade in cardiac myocytes. The potential role of the cascade in the integration of two signaling pathways leading to myocyte hypertrophy. J Biol Chem. 1994 Jan 14;269(2):1110–1119. [PubMed] [Google Scholar]
  4. Bogoyevitch M. A., Glennon P. E., Sugden P. H. Endothelin-1, phorbol esters and phenylephrine stimulate MAP kinase activities in ventricular cardiomyocytes. FEBS Lett. 1993 Feb 15;317(3):271–275. doi: 10.1016/0014-5793(93)81291-7. [DOI] [PubMed] [Google Scholar]
  5. Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. doi: 10.1016/0003-2697(76)90527-3. [DOI] [PubMed] [Google Scholar]
  6. Bruneau B. G., Piazza L. A., de Bold A. J. BNP gene expression is specifically modulated by stretch and ET-1 in a new model of isolated rat atria. Am J Physiol. 1997 Dec;273(6 Pt 2):H2678–H2686. doi: 10.1152/ajpheart.1997.273.6.H2678. [DOI] [PubMed] [Google Scholar]
  7. Bugge E., Ytrehus K. Endothelin-1 can reduce infarct size through protein kinase C and KATP channels in the isolated rat heart. Cardiovasc Res. 1996 Nov;32(5):920–929. [PubMed] [Google Scholar]
  8. Cheng G., Hagen T. P., Dawson M. L., Barnes K. V., Menick D. R. The role of GATA, CArG, E-box, and a novel element in the regulation of cardiac expression of the Na+-Ca2+ exchanger gene. J Biol Chem. 1999 Apr 30;274(18):12819–12826. doi: 10.1074/jbc.274.18.12819. [DOI] [PubMed] [Google Scholar]
  9. Claycomb W. C., Lanson N. A., Jr, Stallworth B. S., Egeland D. B., Delcarpio J. B., Bahinski A., Izzo N. J., Jr HL-1 cells: a cardiac muscle cell line that contracts and retains phenotypic characteristics of the adult cardiomyocyte. Proc Natl Acad Sci U S A. 1998 Mar 17;95(6):2979–2984. doi: 10.1073/pnas.95.6.2979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Crossley M., Orkin S. H. Phosphorylation of the erythroid transcription factor GATA-1. J Biol Chem. 1994 Jun 17;269(24):16589–16596. [PubMed] [Google Scholar]
  11. Fukuda Y., Hirata Y., Taketani S., Kojima T., Oikawa S., Nakazato H., Kobayashi Y. Endothelin stimulates accumulations of cellular atrial natriuretic peptide and its messenger RNA in rat cardiocytes. Biochem Biophys Res Commun. 1989 Nov 15;164(3):1431–1436. doi: 10.1016/0006-291x(89)91830-5. [DOI] [PubMed] [Google Scholar]
  12. Gregory T., Yu C., Ma A., Orkin S. H., Blobel G. A., Weiss M. J. GATA-1 and erythropoietin cooperate to promote erythroid cell survival by regulating bcl-xL expression. Blood. 1999 Jul 1;94(1):87–96. [PubMed] [Google Scholar]
  13. Herzig T. C., Jobe S. M., Aoki H., Molkentin J. D., Cowley A. W., Jr, Izumo S., Markham B. E. Angiotensin II type1a receptor gene expression in the heart: AP-1 and GATA-4 participate in the response to pressure overload. Proc Natl Acad Sci U S A. 1997 Jul 8;94(14):7543–7548. doi: 10.1073/pnas.94.14.7543. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Ito H., Hirata Y., Hiroe M., Tsujino M., Adachi S., Takamoto T., Nitta M., Taniguchi K., Marumo F. Endothelin-1 induces hypertrophy with enhanced expression of muscle-specific genes in cultured neonatal rat cardiomyocytes. Circ Res. 1991 Jul;69(1):209–215. doi: 10.1161/01.res.69.1.209. [DOI] [PubMed] [Google Scholar]
  15. Ito H., Hiroe M., Hirata Y., Fujisaki H., Adachi S., Akimoto H., Ohta Y., Marumo F. Endothelin ETA receptor antagonist blocks cardiac hypertrophy provoked by hemodynamic overload. Circulation. 1994 May;89(5):2198–2203. doi: 10.1161/01.cir.89.5.2198. [DOI] [PubMed] [Google Scholar]
  16. Kaddoura S., Firth J. D., Boheler K. R., Sugden P. H., Poole-Wilson P. A. Endothelin-1 is involved in norepinephrine-induced ventricular hypertrophy in vivo. Acute effects of bosentan, an orally active, mixed endothelin ETA and ETB receptor antagonist. Circulation. 1996 Jun 1;93(11):2068–2079. doi: 10.1161/01.cir.93.11.2068. [DOI] [PubMed] [Google Scholar]
  17. Keinänen R., Vartiainen N., Koistinaho J. Molecular cloning and characterization of the rat inducible nitric oxide synthase (iNOS) gene. Gene. 1999 Jul 8;234(2):297–305. doi: 10.1016/s0378-1119(99)00196-1. [DOI] [PubMed] [Google Scholar]
  18. Kurabayashi M., Komuro I., Shibasaki Y., Tsuchimochi H., Takaku F., Yazaki Y. Functional identification of the transcriptional regulatory elements within the promoter region of the human ventricular myosin alkali light chain gene. J Biol Chem. 1990 Nov 5;265(31):19271–19278. [PubMed] [Google Scholar]
  19. Lee Y., Shioi T., Kasahara H., Jobe S. M., Wiese R. J., Markham B. E., Izumo S. The cardiac tissue-restricted homeobox protein Csx/Nkx2.5 physically associates with the zinc finger protein GATA4 and cooperatively activates atrial natriuretic factor gene expression. Mol Cell Biol. 1998 Jun;18(6):3120–3129. doi: 10.1128/mcb.18.6.3120. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. McWhinney C. D., Hansen C., Robishaw J. D. Alpha-1 adrenergic signaling in a cardiac murine atrial myocyte (HL-1) cell line. Mol Cell Biochem. 2000 Nov;214(1-2):111–119. doi: 10.1023/a:1007129723949. [DOI] [PubMed] [Google Scholar]
  21. Molkentin J. D., Kalvakolanu D. V., Markham B. E. Transcription factor GATA-4 regulates cardiac muscle-specific expression of the alpha-myosin heavy-chain gene. Mol Cell Biol. 1994 Jul;14(7):4947–4957. doi: 10.1128/mcb.14.7.4947. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Molkentin J. D., Lu J. R., Antos C. L., Markham B., Richardson J., Robbins J., Grant S. R., Olson E. N. A calcineurin-dependent transcriptional pathway for cardiac hypertrophy. Cell. 1998 Apr 17;93(2):215–228. doi: 10.1016/s0092-8674(00)81573-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Morimoto T., Hasegawa K., Kaburagi S., Kakita T., Wada H., Yanazume T., Sasayama S. Phosphorylation of GATA-4 is involved in alpha 1-adrenergic agonist-responsive transcription of the endothelin-1 gene in cardiac myocytes. J Biol Chem. 2000 May 5;275(18):13721–13726. doi: 10.1074/jbc.275.18.13721. [DOI] [PubMed] [Google Scholar]
  24. Nicholas S. B., Philipson K. D. Cardiac expression of the Na(+)/Ca(2+) exchanger NCX1 is GATA factor dependent. Am J Physiol. 1999 Jul;277(1 Pt 2):H324–H330. doi: 10.1152/ajpheart.1999.277.1.H324. [DOI] [PubMed] [Google Scholar]
  25. O'Prey J., Ramsay S., Chambers I., Harrison P. R. Transcriptional up-regulation of the mouse cytosolic glutathione peroxidase gene in erythroid cells is due to a tissue-specific 3' enhancer containing functionally important CACC/GT motifs and binding sites for GATA and Ets transcription factors. Mol Cell Biol. 1993 Oct;13(10):6290–6303. doi: 10.1128/mcb.13.10.6290. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Rindt H., Gulick J., Knotts S., Neumann J., Robbins J. In vivo analysis of the murine beta-myosin heavy chain gene promoter. J Biol Chem. 1993 Mar 5;268(7):5332–5338. [PubMed] [Google Scholar]
  27. Shichiri M., Kato H., Marumo F., Hirata Y. Endothelin-1 as an autocrine/paracrine apoptosis survival factor for endothelial cells. Hypertension. 1997 Nov;30(5):1198–1203. doi: 10.1161/01.hyp.30.5.1198. [DOI] [PubMed] [Google Scholar]
  28. Shichiri M., Yokokura M., Marumo F., Hirata Y. Endothelin-1 inhibits apoptosis of vascular smooth muscle cells induced by nitric oxide and serum deprivation via MAP kinase pathway. Arterioscler Thromb Vasc Biol. 2000 Apr;20(4):989–997. doi: 10.1161/01.atv.20.4.989. [DOI] [PubMed] [Google Scholar]
  29. Shubeita H. E., McDonough P. M., Harris A. N., Knowlton K. U., Glembotski C. C., Brown J. H., Chien K. R. Endothelin induction of inositol phospholipid hydrolysis, sarcomere assembly, and cardiac gene expression in ventricular myocytes. A paracrine mechanism for myocardial cell hypertrophy. J Biol Chem. 1990 Nov 25;265(33):20555–20562. [PubMed] [Google Scholar]
  30. Sussman M. A., Lim H. W., Gude N., Taigen T., Olson E. N., Robbins J., Colbert M. C., Gualberto A., Wieczorek D. F., Molkentin J. D. Prevention of cardiac hypertrophy in mice by calcineurin inhibition. Science. 1998 Sep 11;281(5383):1690–1693. doi: 10.1126/science.281.5383.1690. [DOI] [PubMed] [Google Scholar]
  31. Suzuki E., Hirata Y., Kohmoto O., Sugimoto T., Hayakawa H., Matsuoka H., Sugimoto T., Kojima M., Kangawa K., Minamino N. Cellular mechanisms for synthesis and secretion of atrial natriuretic peptide and brain natriuretic peptide in cultured rat atrial cells. Circ Res. 1992 Nov;71(5):1039–1048. doi: 10.1161/01.res.71.5.1039. [DOI] [PubMed] [Google Scholar]
  32. Suzuki T., Miyauchi T. A novel pharmacological action of ET-1 to prevent the cytotoxicity of doxorubicin in cardiomyocytes. Am J Physiol Regul Integr Comp Physiol. 2001 May;280(5):R1399–R1406. doi: 10.1152/ajpregu.2001.280.5.R1399. [DOI] [PubMed] [Google Scholar]
  33. Suzuki Y. J., Mizuno M., Packer L. Signal transduction for nuclear factor-kappa B activation. Proposed location of antioxidant-inhibitable step. J Immunol. 1994 Dec 1;153(11):5008–5015. [PubMed] [Google Scholar]
  34. Thuerauf D. J., Hanford D. S., Glembotski C. C. Regulation of rat brain natriuretic peptide transcription. A potential role for GATA-related transcription factors in myocardial cell gene expression. J Biol Chem. 1994 Jul 8;269(27):17772–17775. [PubMed] [Google Scholar]
  35. Towatari M., May G. E., Marais R., Perkins G. R., Marshall C. J., Cowley S., Enver T. Regulation of GATA-2 phosphorylation by mitogen-activated protein kinase and interleukin-3. J Biol Chem. 1995 Feb 24;270(8):4101–4107. doi: 10.1074/jbc.270.8.4101. [DOI] [PubMed] [Google Scholar]
  36. Wang P., Gallagher K. P., Downey J. M., Cohen M. V. Pretreatment with endothelin-1 mimics ischemic preconditioning against infarction in isolated rabbit heart. J Mol Cell Cardiol. 1996 Mar;28(3):579–588. doi: 10.1006/jmcc.1996.0054. [DOI] [PubMed] [Google Scholar]
  37. Yamazaki T., Komuro I., Kudoh S., Zou Y., Shiojima I., Hiroi Y., Mizuno T., Maemura K., Kurihara H., Aikawa R. Endothelin-1 is involved in mechanical stress-induced cardiomyocyte hypertrophy. J Biol Chem. 1996 Feb 9;271(6):3221–3228. doi: 10.1074/jbc.271.6.3221. [DOI] [PubMed] [Google Scholar]
  38. Yanagisawa M., Kurihara H., Kimura S., Tomobe Y., Kobayashi M., Mitsui Y., Yazaki Y., Goto K., Masaki T. A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature. 1988 Mar 31;332(6163):411–415. doi: 10.1038/332411a0. [DOI] [PubMed] [Google Scholar]
  39. Zhang R., Min W., Sessa W. C. Functional analysis of the human endothelial nitric oxide synthase promoter. Sp1 and GATA factors are necessary for basal transcription in endothelial cells. J Biol Chem. 1995 Jun 23;270(25):15320–15326. doi: 10.1074/jbc.270.25.15320. [DOI] [PubMed] [Google Scholar]

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