The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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Peroxisome proliferator-activated receptor γ is essential for secretion of ANP induced by prostaglandin D2 in the beating rat atrium

  • Zhang, Ying (Department of Physiology, School of Medicine, Yanbian University) ;
  • Li, Xiang (Department of Physiology, School of Medicine, Yanbian University) ;
  • Liu, Li-Ping (Department of Physiology, School of Medicine, Yanbian University) ;
  • Hong, Lan (Department of Physiology, School of Medicine, Yanbian University) ;
  • Liu, Xia (Department of Physiology, School of Medicine, Yanbian University) ;
  • Zhang, Bo (Department of Physiology, School of Medicine, Yanbian University) ;
  • Wu, Cheng-Zhe (Department of Physiology, School of Medicine, Yanbian University) ;
  • Cui, Xun (Department of Physiology, School of Medicine, Yanbian University)
  • Received : 2016.10.17
  • Accepted : 2016.12.12
  • Published : 2017.05.01
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Abstract

Prostaglandin $D_2$ ($PGD_2$) may act against myocardial ischemia-reperfusion (I/R) injury and play an anti-inflammatory role in the heart. Although the effect of $PGD_2$ in regulation of ANP secretion of the atrium was reported, the mechanisms involved are not clearly identified. The aim of the present study was to investigate whether $PGD_2$ can regulate ANP secretion in the isolated perfused beating rat atrium, and its underlying mechanisms. $PGD_2$ (0.1 to $10{\mu}M$) significantly increased atrial ANP secretion concomitantly with positive inotropy in a dose-dependent manner. Effects of $PGD_2$ on atrial ANP secretion and mechanical dynamics were abolished by AH-6809 ($1.0{\mu}M$) and AL-8810 ($1.0{\mu}M$), $PGD_2$ and prostaglandin $F2{\alpha}$ ($PGF2{\alpha}$) receptor antagonists, respectively. Moreover, $PGD_2$ clearly upregulated atrial peroxisome proliferator-activated receptor gamma ($PPAR{\gamma}$) and the $PGD_2$ metabolite 15-deoxy-${\Delta}12$, 14-$PGJ_2$ (15d-$PGJ_2$, $0.1{\mu}M$) dramatically increased atrial ANP secretion. Increased ANP secretions induced by $PGD_2$ and 15d-$PGJ_2$ were completely blocked by the $PPAR{\gamma}$ antagonist GW9662 ($0.1{\mu}M$). PD98059 ($10.0{\mu}M$) and LY294002 ($1.0{\mu}M$), antagonists of mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) and phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) signaling, respectively, significantly attenuated the increase of atrial ANP secretion by $PGD_2$. These results indicated that $PGD_2$ stimulated atrial ANP secretion and promoted positive inotropy by activating $PPAR{\gamma}$ in beating rat atria. MAPK/ERK and PI3K/Akt signaling pathways were each partially involved in regulating $PGD_2$-induced atrial ANP secretion.

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References

  1. Kalra BS, Roy V. Efficacy of metabolic modulators in ischemic heart disease: an overview. J Clin Pharmacol. 2012;52:292-305. https://doi.org/10.1177/0091270010396042
  2. Ryu SK, Mallat Z, Benessiano J, Tedgui A, Olsson AG, Bao W, Schwartz GG, Tsimikas S; Myocardial Ischemia Reduction With Aggressive Cholesterol Lowering (MIRACL) Trial Investigators. Phospholipase A2 enzymes, high-dose atorvastatin, and prediction of ischemic events after acute coronary syndromes. Circulation. 2012;125:757-766. https://doi.org/10.1161/CIRCULATIONAHA.111.063487
  3. Gross GJ, Falck JR, Gross ER, Isbell M, Moore J, Nithipatikom K. Cytochrome P450 and arachidonic acid metabolites: role in myocardial ischemia/reperfusion injury revisited. Cardiovasc Res. 2005;68:18-25. https://doi.org/10.1016/j.cardiores.2005.06.007
  4. Qiu H, Liu JY, Wei D, Li N, Yamoah EN, Hammock BD, Chiamvimonvat N. Cardiac-generated prostanoids mediate cardiac myocyte apoptosis after myocardial ischaemia. Cardiovasc Res. 2012;95:336-345. https://doi.org/10.1093/cvr/cvs191
  5. Ricciotti E, FitzGerald GA. Prostaglandins and inflammation. Arterioscler Thromb Vasc Biol. 2011;31:986-1000. https://doi.org/10.1161/ATVBAHA.110.207449
  6. Taba Y, Sasaguri T, Miyagi M, Abumiya T, Miwa Y, Ikeda T, Mitsumata M. Fluid shear stress induces lipocalin-type prostaglandin D(2) synthase expression in vascular endothelial cells. Circ Res. 2000;86:967-973. https://doi.org/10.1161/01.RES.86.9.967
  7. Zhang X, Young HA. PPAR and immune system--what do we know? Int Immunopharmacol. 2002;2:1029-1044. https://doi.org/10.1016/S1567-5769(02)00057-7
  8. Lim HJ, Lee KS, Lee S, Park JH, Choi HE, Go SH, Kwak HJ, Park HY. 15d-PGJ2 stimulates HO-1 expression through p38 MAP kinase and Nrf-2 pathway in rat vascular smooth muscle cells. Toxicol Appl Pharmacol. 2007;223:20-27. https://doi.org/10.1016/j.taap.2007.04.019
  9. Lee SJ, Kim MS, Park JY, Woo JS, Kim YK. 15-Deoxy-delta 12,14-prostaglandin J2 induces apoptosis via JNK-mediated mitochondrial pathway in osteoblastic cells. Toxicology. 2008;248:121-129. https://doi.org/10.1016/j.tox.2008.03.014
  10. Jung WK, Park IS, Park SJ, Yea SS, Choi YH, Oh S, Park SG, Choi IW. The 15-deoxy-Delta12,14-prostaglandin J2 inhibits LPS-stimulated AKT and NF-kappaB activation and suppresses interleukin-6 in osteoblast-like cells MC3T3E-1. Life Sci. 2009;85:46-53. https://doi.org/10.1016/j.lfs.2009.04.010
  11. Giri S, Rattan R, Singh AK, Singh I. The 15-deoxy-delta12,14-prostaglandin J2 inhibits the inflammatory response in primary rat astrocytes via down-regulating multiple steps in phosphatidylinositol 3-kinase-Akt-NF-kappaB-p300 pathway independent of peroxisome proliferator-activated receptor gamma. J Immunol. 2004;173:5196-5208. https://doi.org/10.4049/jimmunol.173.8.5196
  12. Bai G, Gao S, Shah A, Yuan K, Park WH, Kim SH. Regulation of ANP secretion from isolated atria by prostaglandins and cyclooxygenase-2. Peptides. 2009;30:1720-1728. https://doi.org/10.1016/j.peptides.2009.06.011
  13. Koyani CN, Windischhofer W, Rossmann C, Jin G, Kickmaier S, Heinzel FR, Groschner K, Alavian-Ghavanini A, Sattler W, Malle E. 15-deoxy-D12,14-PGJ2 promotes inflammation and apoptosis in cardiomyocytes via the DP2/MAPK/TNFa axis. Int J Cardiol. 2014;173:472-480. https://doi.org/10.1016/j.ijcard.2014.03.086
  14. Sawyer N, Cauchon E, Chateauneuf A, Cruz RP, Nicholson DW, Metters KM, O'Neill GP, Gervais FG. Molecular pharmacology of the human prostaglandin D2 receptor, CRTH2. Br J Pharmacol. 2002;137:1163-1172. https://doi.org/10.1038/sj.bjp.0704973
  15. Cho KW, Lee SJ, Wen JF, Kim SH, Seul KH, Lee HS. Mechanical control of extracellular space in rabbit atria: an intimate modulator of the translocation of extracellular fluid and released atrial natriuretic peptide. Exp Physiol. 2002;87:185-194. https://doi.org/10.1113/eph8702302
  16. Katsumata Y, Shinmura K, Sugiura Y, Tohyama S, Matsuhashi T, Ito H, Yan X, Ito K, Yuasa S, Ieda M, Urade Y, Suematsu M, Fukuda K, Sano M. Endogenous prostaglandin D2 and its metabolites protect the heart against ischemia-reperfusion injury by activating Nrf2. Hypertension. 2014;63:80-87. https://doi.org/10.1161/HYPERTENSIONAHA.113.01639
  17. Kim KH, Sadikot RT, Xiao L, Christman JW, Freeman ML, Chan JY, Oh YK, Blackwell TS, Joo M. Nrf2 is essential for the expression of lipocalin-prostaglandin D synthase induced by prostaglandin D2. Free Radic Biol Med. 2013;65:1134-1142. https://doi.org/10.1016/j.freeradbiomed.2013.08.192
  18. Zhang QL, Cui BR, Li HY, Li P, Hong L, Liu LP, Ding DZ, Cui X. MAPK and PI3K pathways regulate hypoxia-induced atrial natriuretic peptide secretion by controlling HIF-1 alpha expression in beating rabbit atria. Biochem Biophys Res Commun. 2013;438:507-512. https://doi.org/10.1016/j.bbrc.2013.07.106
  19. Liu LP, Hong L, Yu L, Li HY, Ding DZ, Jin SJ, Cui X. Ouabain stimulates atrial natriuretic peptide secretion via the endothelin-1/ET(B) receptor-mediated pathway in beating rabbit atria. Life Sci. 2012;90:793-798. https://doi.org/10.1016/j.lfs.2012.04.008
  20. Mitaka C, Si MK, Tulafu M, Yu Q, Uchida T, Abe S, Kitagawa M, Ikeda S, Eishi Y, Tomita M. Effects of atrial natriuretic peptide on inter-organ crosstalk among the kidney, lung, and heart in a rat model of renal ischemia-reperfusion injury. Intensive Care Med Exp. 2014;2:28. https://doi.org/10.1186/s40635-014-0028-8
  21. Hong L, Xi J, Zhang Y, Tian W, Xu J, Cui X, Xu Z. Atrial natriuretic peptide prevents the mitochondrial permeability transition pore opening by inactivating glycogen synthase kinase $3{\beta}$ via PKG and PI3K in cardiac H9c2 cells. Eur J Pharmacol. 2012;695:13-19. https://doi.org/10.1016/j.ejphar.2012.07.053
  22. Kiemer AK, Hartung T, Vollmar AM. cGMP-mediated inhibition of TNF-alpha production by the atrial natriuretic peptide in murine macrophages. J Immunol. 2000;165:175-181. https://doi.org/10.4049/jimmunol.165.1.175
  23. Kiemer AK, Weber NC, Furst R, Bildner N, Kulhanek-Heinze S, Vollmar AM. Inhibition of p38 MAPK activation via induction of MKP-1: atrial natriuretic peptide reduces TNF-alpha-induced actin polymerization and endothelial permeability. Circ Res. 2002;90:874-881. https://doi.org/10.1161/01.RES.0000017068.58856.F3
  24. Ladetzki-Baehs K, Keller M, Kiemer AK, Koch E, Zahler S, Wendel A, Vollmar AM. Atrial natriuretic peptide, a regulator of nuclear factor-kappaB activation in vivo. Endocrinology. 2007;148:332-336. https://doi.org/10.1210/en.2006-0935

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