Dehydroepiandrosterone inhibits the Src/STAT3 constitutive activation in pulmonary arterial hypertension

American Journal of Physiology - Heart and Circulatory Physiology

Volumn 301, Issue 5, 2011, Pages

  Paulin, Roxane ^a   Meloche, Jolyane ^a   Jacob, Maria Helena ^a   Bisserier, Malik ^b   Courboulin, Audrey ^a   Bonnet, Sébastien ^a  

^a LAVAL UNIVERSITY   (Canada)

^b UNIVERSITÉ DE BORDEAUX   (France)

Author keywords

Apoptosis; Proliferation; Remodeling; Signal transducer and activator of transcription 3; Therapies

Indexed keywords

BONE MORPHOGENETIC PROTEIN RECEPTOR 2; CALCIUM ION; MICRORNA; PRASTERONE; PROTEIN KINASE PIM 1; PROTEIN TYROSINE KINASE; STAT3 PROTEIN; SURVIVIN; TRANSCRIPTION FACTOR NFAT; TRANSCRIPTION FACTOR NFATC2; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; APOPTOSIS; ARTICLE; CALCIUM CELL LEVEL; CELL PROLIFERATION; CONTROLLED STUDY; DOWN REGULATION; HEART RIGHT VENTRICLE HYPERTROPHY; HISTOLOGY; HUMAN; HUMAN CELL; LUNG; LUNG ARTERY PRESSURE; MITOCHONDRIAL MEMBRANE POTENTIAL; NICK END LABELING; NONHUMAN; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN EXPRESSION; PULMONARY ARTERY; PULMONARY HYPERTENSION; RAT; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; SMOOTH MUSCLE FIBER; T LYMPHOCYTE; UPREGULATION; WESTERN BLOTTING;

ADULT; ANIMALS; ANTIHYPERTENSIVE AGENTS; APOPTOSIS; BLOTTING, WESTERN; BONE MORPHOGENETIC PROTEIN RECEPTORS, TYPE II; CALCIUM; CELL PROLIFERATION; CELLS, CULTURED; DEHYDROEPIANDROSTERONE; DISEASE MODELS, ANIMAL; ENZYME ACTIVATION; FEMALE; HUMANS; HYPERTENSION, PULMONARY; IN SITU NICK-END LABELING; INHIBITOR OF APOPTOSIS PROTEINS; MALE; MEMBRANE POTENTIAL, MITOCHONDRIAL; MICRORNAS; MICROTUBULE-ASSOCIATED PROTEINS; MIDDLE AGED; MONOCROTALINE; MUSCLE, SMOOTH; MYOCYTES, SMOOTH MUSCLE; NFATC TRANSCRIPTION FACTORS; PROTO-ONCOGENE PROTEINS C-PIM-1; PULMONARY ARTERY; RATS; RATS, SPRAGUE-DAWLEY; REAL-TIME POLYMERASE CHAIN REACTION; SIGNAL TRANSDUCTION; SRC-FAMILY KINASES; STAT3 TRANSCRIPTION FACTOR; VASODILATOR AGENTS;

EID: 80355128997     PISSN: 03636135     EISSN: 15221539     Source Type: Journal    
DOI: 10.1152/ajpheart.00654.2011     Document Type: Article

References (60)

1. Anonymous. World Medical Association Declaration of Helsinki. Recommendations guiding physicians in biomedical research involving human subjects. Cardiovasc Res 35: 2-3, 1997.
2. Abe K, Toba M, Alzoubi A, Ito M, Fagan KA, Cool CD, Voelkel NF, McMurtry IF, Oka M. Formation of plexiform lesions in experimental severe pulmonary arterial hypertension. Circulation 121: 2747-2754, 2010.
3. + channels as a new mechanism of agonist-induced vasoconstriction. Proc Natl Acad Sci USA 99: 14560-14565, 2002.
4. Archer S, Rich S. Primary pulmonary hypertension: a vascular biology and translational research "Work in progress". Circulation 102: 2781-2791, 2000.
5. Aznar S, Valeron PF, del Rincon SV, Perez LF, Perona R, Lacal JC. Simultaneous tyrosine and serine phosphorylation of STAT3 transcription factor is involved in Rho A GTPase oncogenic transformation. Mol Biol Cell 12: 3282-3294, 2001.
6. Banes-Berceli AK, Ketsawatsomkron P, Ogbi S, Patel B, Pollock DM, Marrero MB. Angiotensin II and endothelin-1 augment the vascular complications of diabetes via JAK2 activation. Am J Physiol Heart Circ Physiol 293: H1291-H1299, 2007.
7. + channel axis is suppressed in cancer and its normalization promotes apoptosis and inhibits cancer growth. Cancer Cell 11: 37-51, 2007.
8. Bonnet S, Dumas-de-La-Roque E, Begueret H, Marthan R, Fayon M, Dos Santos P, Savineau JP, Baulieu EE. Dehydroepiandrosterone (DHEA) prevents and reverses chronic hypoxic pulmonary hypertension. Proc Natl Acad Sci USA 100: 9488-9493, 2003. 9.
9. Bonnet S, Paulin R, Sutendra G, Dromparis P, Roy M, Watson KO, Nagendran J, Haromy A, Dyck JR, Michelakis ED. Dehydroepiandro-sterone reverses systemic vascular remodeling through the inhibition of the Akt/GSK3-fj/NFAT axis. Circulation 120: 1231-1240, 2009.
10. Bonnet S, Rochefort G, Sutendra G, Archer SL, Haromy A, Webster L, Hashimoto K, Bonnet SN, Michelakis ED. The nuclear factor of activated T cells in pulmonary arterial hypertension can be therapeutically targeted. Proc Natl Acad Sci USA 104: 11418-11423, 2007.
11. Brock M, Trenkmann M, Gay RE, Michel BA, Gay S, Fischler M, Ulrich S, Speich R, Huber LC. Interleukin-6 modulates the expression of the bone morphogenic protein receptor type II through a novel STAT3-microRNA cluster 17/92 pathway. Circ Res 104: 1184-1191, 2009.
12. Courboulin A, Paulin R, Giguere NJ, Saksouk N, Perreault T, Me-loche J, Paquet ER, Biardel S, Provencher S, Cote J, Simard MJ, Bonnet S. Role for miR-204 in human pulmonary arterial hypertension. J Exp Med 208: 535-548, 2011.
13. Csiszar A, Labinskyy N, Olson S, Pinto JT, Gupte S, Wu JM, Hu F, Ballabh P, Podlutsky A, Losonczy G, de Cabo R, Mathew R, Wolin MS, Ungvari Z. Resveratrol prevents monocrotaline-induced pulmonary hypertension in rats. Hypertension 54: 668-675, 2009.
14. Darnell JE Jr. STATs and gene regulation. Science 277: 1630-1635, 1997.
15. de Frutos S, Caldwell E, Nitta CH, Kanagy NL, Wang J, Wang W, Walker MK, Gonzalez Bosc LV. NFATc3 contributes to intermittent hypoxia-induced arterial remodeling in mice. Am J Physiol Heart Circ Physiol 299: H356-H363, 2010.
16. de Frutos S, Ramiro-Diaz JM, Nitta CH, Sherpa ML, Gonzalez Bosc LV. Endothelin-1 contributes to increased NFATc3 activation by chronic hypoxia in pulmonary arteries. Am J Physiol Cell Physiol 301: C441-C450, 2011.
17. 2+ channels. Am J Physiol Cell Physiol 300: C576-C587, 2011.
18. Dumas de la Roque E, Savineau JP, Bonnet S. Dehydroepiandrosterone: a new treatment for vascular remodeling diseases including pulmonary arterial hypertension. Pharmacol Ther 126: 186-199, 2010.
19. Ehrmann J, Strakova N, Vrzalikova K, Hezova R, Kolar Z. Expression of STATs and their inhibitors SOCS and PIAS in brain tumors. In vitro and in vivo study. Neoplasma 55: 482-487, 2008.
20. +-channel opener. Am J Physiol Lung Cell Mol Physiol 274: L186-L195, 1998.
21. Frasch HF, Marshall C, Marshall BE. Endothelin-1 is elevated in monocrotaline pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol 276: L304-L310, 1999.
22. Glienke W, Maute L, Wicht J, Bergmann L. Curcumin inhibits constitutive STAT3 phosphorylation in human pancreatic cancer cell lines and downregulation of survivin/BIRC5 gene expression. Cancer Invest 28: 166-171, 2010.
23. Gough DJ, Corlett A, Schlessinger K, Wegrzyn J, Larner AC, Levy DE. Mitochondrial STAT3 supports Ras-dependent oncogenic transformation. Science 324: 1713-1716, 2009.
24. Hansmann G, Wagner RA, Schellong S, Perez VA, Urashima T, Wang L, Sheikh AY, Suen RS, Stewart DJ, Rabinovitch M. Pulmonary arterial hypertension is linked to insulin resistance and reversed by peroxisome proliferator-activated receptor-gamma activation. Circulation 115: 1275-1284, 2007.
25. Hofmann F, Feil R, Kleppisch T, Schlossmann J. Function of cGMP-dependent protein kinases as revealed by gene deletion. Physiol Rev 86: 1-23, 2006.
26. Homma N, Nagaoka T, Karoor V, Imamura M, Taraseviciene-Stewart L, Walker LA, Fagan KA, McMurtry IF, Oka M. Involvement of RhoA/Rho kinase signaling in protection against monocrotaline-induced pulmonary hypertension in pneumonectomized rats by dehydroepiandrosterone. Am J Physiol Lung Cell Mol Physiol 295: L71-L78, 2008.
27. Hu XF, Li J, Vandervalk S, Wang Z, Magnuson NS, Xing PX. PIM-1-specific mAb suppresses human and mouse tumor growth by decreasing PIM-1 levels, reducing Akt phosphorylation, and activating apoptosis. J Clin Invest 119: 362-375, 2009.
28. 2+ channels in rabbit colonic smooth muscle cells by c-Src and focal adhesion kinase. J Biol Chem 273: 5337-5342, 1998.
29. Humbert M, Morrell NW, Archer SL, Stenmark KR, MacLean MR, Lang IM, Christman BW, Weir EK, Eickelberg O, Voelkel NF, Rabinovitch M. Cellular and molecular pathobiology of pulmonary arterial hypertension. J Am Coll Cardiol 43: 13S-2-4S, 2004.
30. Jahn MP, Jacob MH, Gomes LF, Duarte R, Araujo AS, Bello-Klein A, Ribeiro MF, Kucharski LC. The effect of long-term DHEA treatment on glucose metabolism, hydrogen peroxide and thioredoxin levels in the skeletal muscle of diabetic rats. J Steroid Biochem Mol Biol 120: 38-44, 2010.
31. Ji JD, Kim HJ, Rho YH, Choi SJ, Lee YH, Cheon HJ, Sohn J, Song GG. Inhibition of IL-10-induced STAT3 activation by 15-deoxy-delta12,14-prostaglandin J2. Rheumatology (Oxford) 44: 983-988, 2005.
32. Juurlink DN, Gomes T, Lipscombe LL, Austin PC, Hux JE, Mamdani MM. Adverse cardiovascular events during treatment with pioglitazone and rosiglitazone: population based cohort study. BMJ 339: b2942, 2009.
33. Kim HJ, Rho YH, Choi SJ, Lee YH, Cheon H, Um JW, Sohn J, Song GG, Ji JD. 15-Deoxy-delta12, 14-PGJ2 inhibits IL-6-induced Stat3 phosphorylation in lymphocytes. Exp Mol Med 37: 179-185, 2005.
34. Kopplow K, Wayss K, Enzmann H, Mayer D. Dehydroepiandrosterone causes hyperplasia and impairs regeneration in rat liver. Int J Oncol 27: 1551-1558, 2005.
35. Li J, Piao YF, Jiang Z, Chen L, Sun HB. Silencing of signal transducer and activator of transcription 3 expression by RNA interference suppresses growth of human hepatocellular carcinoma in tumor-bearing nude mice. World J Gastroenterol 15: 2602-2608, 2009.
36. Lin MT, Lin BR, Chang CC, Chu CY, Su HJ, Chen ST, Jeng YM, Kuo ML. IL-6 induces AGS gastric cancer cell invasion via activation of the c-Src/RhoA/ROCK signaling pathway. Int J Cancer 120: 2600-2608, 2007.
37. Masri FA, Xu W, Comhair SA, Asosingh K, Koo M, Vasanji A, Drazba J, Anand-Apte B, Erzurum SC. Hyperproliferative apoptosis-resistant endothelial cells in idiopathic pulmonary arterial hypertension. Am J Physiol Lung Cell Mol Physiol 293: L548-L554, 2007.
38. McMurtry MS, Archer SL, Altieri DC, Bonnet S, Haromy A, Harry G, Bonnet S, Puttagunta L, Michelakis ED. Gene therapy targeting survivin selectively induces pulmonary vascular apoptosis and reverses pulmonary arterial hypertension. J Clin Invest 115: 1479-1491, 2005.
39. McMurtry MS, Archer SL, Altieri DC, Bonnet S, Haromy A, Harry G, Puttagunta L, Michelakis ED. Gene therapy targeting survivin selectively induces pulmonary vascular apoptosis and reverses pulmonary arterial hypertension. J Clin Invest 115: 1479-1491, 2005.
40. Meloche J, Paulin R, Courboulin A, Lambert C, Barrier M, Bonnet P, Bisserier M, Roy M, Sussman MA, Agharazii M, Bonnet S. RAGE-dependent activation of the oncoprotein pim1 plays a critical role in systemic vascular remodeling processes. Arterioscler Thromb Vasc Biol 31: 2114-2124, 2011.
41. Mukhopadhyay S, Shah M, Xu F, Patel K, Tuder RM, Sehgal PB. Cytoplasmic provenance of STAT3 and PY-STAT3 in the endolysosomal compartments in pulmonary arterial endothelial and smooth muscle cells: implications in pulmonary arterial hypertension. Am J Physiol Lung Cell Mol Physiol 294: L449-L468, 2008.
42. Muraski JA, Fischer KM, Wu W, Cottage CT, Quijada P, Mason M, Din S, Gude N, Alvarez R Jr, Rota M, Kajstura J, Wang Z, Schaefer E, Chen X, MacDonnel S, Magnuson N, Houser SR, Anversa P, Sussman MA. Pim-1 kinase antagonizes aspects of myocardial hypertrophy and compensation to pathological pressure overload. Proc Natl Acad Sci USA 105: 13889-13894, 2008.
43. Muraski JA, Rota M, Misao Y, Fransioli J, Cottage C, Gude N, Esposito G, Delucchi F, Arcarese M, Alvarez R, Siddiqi S, Emmanuel GN, Wu W, Fischer K, Martindale JJ, Glembotski CC, Leri A, Kajstura J, Magnuson N, Berns A, Beretta RM, Houser SR, Schaefer EM, Anversa P, Sussman MA. Pim-1 regulates cardiomyocyte survival downstream of Akt. Nat Med 13: 1467-1475, 2007.
44. Nitabach MN, Llamas DA, Thompson IJ, Collins KA, Holmes TC. Phosphorylation-dependent and phosphorylation-independent modes of modulation of shaker family voltage-gated potassium channels by SRC family protein tyrosine kinases. J Neurosci 22: 7913-7922, 2002.
45. Oka M, Karoor V, Homma N, Nagaoka T, Sakao E, Golembeski SM, Limbird J, Imamura M, Gebb SA, Fagan KA, McMurtry IF. Dehydroepiandrosterone upregulates soluble guanylate cyclase and inhibits hypoxic pulmonary hypertension. Cardiovasc Res 74: 377-387, 2007.
46. Paulin R, Courboulin A, Meloche J, Mainguy V, Dumas de la Roque E, Saksouk N, Cote J, Provencher S, Sussman MA, Bonnet S. Signal transducers and activators of transcription-3/pim1 axis plays a critical role in the pathogenesis of human pulmonary arterial hypertension. Circulation 123: 1205-1215, 2011.
47. + channels of hypoxic human pulmonary vascular cells. Am J Respir Cell Mol Biol 20: 737-745, 1999.
48. Poczatkova H, Bogdanova K, Uherkova L, Cervenkova K, Riegrova D, Rypka M, Vesely J. Dehydroepiandrosterone effects on the mRNA levels of peroxisome proliferator-activated receptors and their coactivators in human hepatoma HepG2 cells. Gen Physiol Biophys 26: 268-274, 2007.
49. Savale L, Tu L, Rideau D, Izziki M, Maitre B, Adnot S, Eddahibi S. Impact of interleukin-6 on hypoxia-induced pulmonary hypertension and lung inflammation in mice. Respir Res 10: 6, 2009.
50. Schermuly RT, Dony E, Ghofrani HA, Pullamsetti S, Savai R, Roth M, Sydykov A, Lai YJ, Weissmann N, Seeger W, Grimminger F. Reversal of experimental pulmonary hypertension by PDGF inhibition. J Clin Invest 115: 2811-2821, 2005.
51. Soon E, Holmes AM, Treacy CM, Doughty NJ, Southgate L, Machado RD, Trembath RC, Jennings S, Barker L, Nicklin P, Walker C, Budd DC, Pepke-Zaba J, Morrell NW. Elevated levels of inflammatory cytokines predict survival in idiopathic and familial pulmonary arterial hypertension. Circulation 122: 920-927, 2010.
52. Sussman MA. Mitochondrial integrity: preservation through Akt/Pim-1 kinase signaling in the cardiomyocyte. Expert Rev Cardiovasc Ther 7: 929-938, 2009.
53. Sutendra G, Bonnet S, Rochefort G, Haromy A, Folmes KD, Lopas-chuk GD, Dyck JR, Michelakis ED. Fatty acid oxidation and malonyl-CoA decarboxylase in the vascular remodeling of pulmonary hypertension. Sci Transl Med 2: 44ra58.
54. Tada Y, Majka S, Carr M, Harral J, Crona D, Kuriyama T, West J. Molecular effects of loss of BMPR2 signaling in smooth muscle in a transgenic mouse model of PAH. Am J Physiol Lung Cell Mol Physiol 292: L1556-L1563, 2007.
55. 2+ channels in chicken nodose neurons. J Neuro-chem 108: 246-259, 2009.
56. Wang LH, Yang XY, Zhang X, Huang J, Hou J, Li J, Xiong H, Mihalic K, Zhu H, Xiao W, Farrar WL. Transcriptional inactivation of STAT3 by PPARgamma suppresses IL-6-responsive multiple myeloma cells. Immunity 20: 205-218, 2004.
57. Wong WK, Knowles JA, Morse JH. Bone morphogenetic protein receptor type II C-terminus interacts with c-Src: implication for a role in pulmonary arterial hypertension. Am J Respir Cell Mol Biol 33: 438-446, 2005.
58. Zakrzewicz A, Hecker M, Marsh LM, Kwapiszewska G, Nejman B, Long L, Seeger W, Schermuly RT, Morrell NW, Morty RE, Eickel-berg O. Receptor for activated C-kinase 1, a novel interaction partner of type II bone morphogenetic protein receptor, regulates smooth muscle cell proliferation in pulmonary arterial hypertension. Circulation 115: 2957-2968, 2007.
59. Zamzami N, Kroemer G. The mitochondrion in apoptosis: how Pandora's box opens. Nat Rev Mol Cell Biol 2: 67-71, 2001.
60. Zhong Z, Wen Z, Darnell JE Jr. Stat3: a STAT family member activated by tyrosine phosphorylation in response to epidermal growth factor and interleukin-6. Science 264: 95-98, 1994.