Relaxin Protects Rat Lungs from Ischemia-Reperfusion Injury via Inducible NO Synthase: Role of ERK-1/2, PI3K, and Forkhead Transcription Factor FKHRL1

PLoS ONE

Volumn 8, Issue 9, 2013, Pages

  Alexiou, Konstantin ^a   Wilbring, Manuel ^a   Matschke, Klaus ^a   Dschietzig, Thomas ^b,c  

^a University Heart Center Dresden   (Germany)

^b IMMUNDIAGNOSTIK AG   (Germany)

^c CHARITÉ UNIVERSITÄTSMEDIZIN BERLIN   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

2 (2 AMINO 3 METHOXYPHENYL)CHROMONE; 4 (1,3 BENZODIOXOL 5 YL) 1 [(2,6 DIETHYLPHENYL)CARBAMOYLMETHYL] 2 (4 PROPOXYPHENYL) 3 PYRROLIDINECARBOXYLIC ACID; ENDOTHELIAL NITRIC OXIDE SYNTHASE; ENDOTHELIN 1; INDUCIBLE NITRIC OXIDE SYNTHASE; KT 5720; LEUKOCYTE ELASTASE; MALONALDEHYDE; MESSENGER RNA; MIFEPRISTONE; MITOGEN ACTIVATED PROTEIN KINASE 1; MITOGEN ACTIVATED PROTEIN KINASE 3; MYELOPEROXIDASE; N [2 (4 BROMOCINNAMYLAMINO)ETHYL] 5 ISOQUINOLINESULFONAMIDE; N [3 (AMINOMETHYL)BENZYL]ACETAMIDINE; N(G) NITROARGININE METHYL ESTER; NITRIC OXIDE SYNTHASE; PHOSPHATIDYLINOSITOL 3 KINASE; RELAXIN; TRANSCRIPTION FACTOR FKHRL1; WORTMANNIN;

ANIMAL CELL; ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; ENDOTHELIUM CELL; ENZYME ACTIVITY; ENZYME INDUCTION; GENE EXPRESSION; ISOLATED LUNG; LUNG ARTERY PRESSURE; LUNG BLOOD VESSEL; LUNG ENDOTHELIUM; LUNG INJURY; LUNG PERFUSION; MALE; NONHUMAN; NOS GENE; ORGAN PRESERVATION; PHYSICAL PARAMETERS; PROTECTION; PROTEIN ANALYSIS; PROTEIN FUNCTION; PROTEIN PHOSPHORYLATION; PROTEIN SECRETION; RAT; REGULATORY MECHANISM; REPERFUSION INJURY; SIGNAL TRANSDUCTION; SMOOTH MUSCLE FIBER; WET TO DRY WEIGHT RATIO;

ANIMALS; BLOOD PRESSURE; FORKHEAD TRANSCRIPTION FACTORS; GENE EXPRESSION REGULATION; LEUKOCYTE ELASTASE; LUNG; MALONDIALDEHYDE; MAP KINASE SIGNALING SYSTEM; NITRIC OXIDE SYNTHASE; PEROXIDASE; PHOSPHATIDYLINOSITOL 3-KINASES; PULMONARY ARTERY; RATS; RELAXIN; REPERFUSION INJURY; VASCULAR RESISTANCE;

EID: 84884786369     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0075592     Document Type: Article

References (32)

1. Whitson BA, Prekker ME, Herrington CS, Whelan TP, Radosevich DM, et al. (2007) Primary graft dysfunction and long-term pulmonary function after lung transplantation. J Heart Lung Transplant 26: 1004-1011.
2. Sedoris KC, Ovechkin AV, Gozal E, Roberts AM, (2009) Differential effects of nitric oxide synthesis on pulmonary vascular function during lung ischemia-reperfusion injury. Arch Physiol Biochem 115: 34-46.
3. Alexiou K, Matschke K, Westphal A, Stangl K, Dschietzig T, (2010) Relaxin is a candidate drug for lung preservation: relaxin-induced protection of rat lungs from ischemia-reperfusion injury. J Heart Lung Transplant 29: 454-460.
4. Garvey EP, Oplinger JA, Furfine ES, Kiff RJ, Laszlo F, et al. (1997) 1400W is a slow, tight binding, and highly selective inhibitor of inducible nitric-oxide synthase in vitro and in vivo. J Biol Chem 272: 4959-4963.
5. Ichihara A, Inscho EW, Imig JD, Navar LG, (1998) Neuronal nitric oxide synthase modulates rat renal microvascular function. Am J Physiol 274: 516-524.
6. Dudley DT, Pang L, Decker SJ, Bridges AJ, Saltiel AR, (1995) A synthetic inhibitor of the mitogen-activated protein kinase cascade. Proc Natl Acad Sci USA 92: 7686-7689.
7. Bourgeois S, Pfahl M, Baulieu EE, (1984) DNA binding properties of glucocorticosteroid receptors bound to the steroid antagonist RU-486. EMBO J 3: 751-755.
8. von Geldern TW, Tasker AS, Sorensen BK, Winn M, Szczepankiewicz BG, et al. (1999) Pyrrolidine-3-carboxylic acids as endothelin antagonists. 4. Side chain conformational restriction leads to ET(B) selectivity. J Med Chem 42: 3668-3678.
9. Murray AJ, (2008) Pharmaological PKA inhibition: all may not be what it seems. Sci Signal 1: re4.
10. Okada S, Saito M, Kazuyama E, Hanada T, Kawaba Y, et al. (2008) Effects of N-hexacosanol on nitric oxide synthase system in diabetic rat nephropathy. Mol Cell Biochem 315: 169-177.
11. Dschietzig T, Brecht A, Bartsch C, Baumann G, Stangl K, et al. (2012) Relaxin improves TNF-α-induced endothelial dysfunction: the role of glucocorticoid receptor and phosphatidylinositol 3-kinase signalling. Cardiovasc Res 95): 97-107.
12. Dahan D, Ducret T, Quignard JF, Marthan R, Savineau JP, et al. (2012) Implication of the ryanodine receptor in TRPV4-induced calcium response in pulmonary arterial smooth muscle cells from normoxic and chronically hypoxic rats. Am J Physiol Lung Cell Mol Physiol 303: L824-L833.
13. Kristof AS, Fielhaber J, Triantafillopoulos A, Nemoto S, Moss J, (2006) Phosphatidylinositol 3-kinase-dependent suppression of the human inducible nitric-oxide synthase promoter is mediated by FKHRL1.J Biol Chem. 281): 23958-23968.
14. Dschietzig T, Bartsch C, Richter C, Laule M, Baumann G, et al. (2003) Relaxin, a pregnancy hormone, is a functional endothelin-1 antagonist: attenuation of endothelin-1-mediated vasoconstriction by stimulation of endothelin type-B receptor expression via ERK-1/2 and nuclear factor-κβ. Circ Res 92: 32-40.
15. Jeyabalan A, Novak J, Danielson LA, Kerchner LJ, Opett SL, et al. (2003) Essential role for vascular gelatinase activity in relaxin-induced renal vasodilation, hyperfiltration, and reduced myogenic reactivity of small arteries. Circ Res 93: 1249-1257.
16. Bathgate R, Halls M, van der Westhuizen E, Callander G, Kocan M, et al. (2013) Relaxin family peptides and their receptors. Physiol Rev 93: 405-480.
17. Masini E, Bani D, Bello MG, Bigazzi M, Mannaioni PF, et al. (1997) Relaxin counteracts myocardial damage induced by ischemia-reperfusion in isolated guinea pig hearts: evidence for an involvement of nitric oxide. Endocrinology 138: 4713-4720.
18. Masini E, Zagli G, Ndisang JF, Solazzo M, Mannaioni PF, et al. (2002) Protective effect of relaxin in cardiac anaphylaxis: involvement of the nitric oxide pathway. Br J Pharmacol 137: 337-344.
19. Perna AM, Masini E, Nistri S, Briganti V, Chiappini L, et al. (2005) Novel drug development opportunity for relaxin in acute myocardial infarction: evidences from a swine model. FASEB J 19: 1525-1527.
20. Dschietzig T, Bartsch C, Stangl V, Baumann G, Stangl K, (2004) Identification of the pregnancy hormone relaxin as glucocorticoid receptor agonist. FASEB J 18: 1536-1538.
21. Kleinert H, Schwarz PM, Förstermann U, (2003) Regulation of the expression of inducible nitric oxide synthase. Biol Chem 384: 1343-1364.
22. Parviz M, Bousamra M 2nd, Chammas JH, Birks EK, Presberg KW, et al. (1999) Effects of chronic pulmonary overcirculation on pulmonary vasomotor tone. Ann Thorac Surg 67: 522-527.
23. Morris SM Jr, Billiar TR, (1994) New insights into the regulation of inducible nitric oxide synthesis. Am J Physiol 266: E829-E839.
24. Beckman JS, Koppenol WH, (1996) Nitric oxide, superoxide, and peroxynitrite: the good, the bad, and ugly. Am J Physiol 271: C1424-C1437.
25. Förstermann U, (2010) Nitric oxide and oxidative stress in vascular disease. Pflugers Arch 459: 923-939.
26. Failli P, Nistri S, Quattrone S, Mazzetti L, Bigazzi M, et al. (2002) Relaxin up-regulates inducible nitric oxide synthase expression and nitric oxide generation in rat coronary endothelial cells. FASEB J 16: 252-254.
27. Kanno S, Lee PC, Zhang Y, Ho C, Griffith BP, et al. (2000) Attenuation of myocardial ischemia/reperfusion injury by superinduction of inducible nitric oxide synthase. Circulation 101: 2742-2748.
28. Colasanti M, Suzuki H, (2000) The dual personality of NO. Trends Pharmacol Sci. 21: 249-252.
29. Zhang H, Park Y, Wu J, Chen X, Lee S, et al. (2009) Role of TNF-alpha in vascular dysfunction. Clin Sci (Lond) 116: 219-230.
30. Brunner F, Brás-Silva C, Cerdeira AS, Leite-Moreira AF, (2006) Cardiovascular endothelins: essential regulators of cardiovascular homeostasis. Pharmacol Ther 111: 508-531.
31. Qian Z, Gelzer-Bell R, Yang SX, Cao W, Ohnishi T, et al. (2001) Inducible nitric oxide synthase inhibition of weibel-palade body release in cardiac transplant rejection. Circulation 104: 2369-2375.
32. Bahrami S, Yu YH, Redl H, Schlag G, (1995) Acute lung injury by endotoxin-induced mediators: prevention by HWA 138, a new xanthine derivative. J Lab Clin Med 125: 487-492.