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Molecular and Cellular Biochemistry

, Volume 438, Issue 1–2, pp 97–109 | Cite as

Role of curcumin in PLD activation by Arf6-cytohesin1 signaling axis in U46619-stimulated pulmonary artery smooth muscle cells

  • Sajal ChakrabortiEmail author
  • Jaganmay Sarkar
  • Rajabrata Bhuyan
  • Tapati Chakraborti
Article

Abstract

Phospholipase D (PLD) catalyzes the hydrolysis of phosphatidylcholine to produce phosphatidic acid (PA) which in some cell types play a pivotal role in agonist-induced increase in NADPH oxidase-derived \( {\text{O}}_{2}^{{ \cdot - }} \)production. Involvement of ADP ribosylation factor (Arf) in agonist-induced activation of PLD is known for smooth muscle cells of systemic arteries, but not in pulmonary artery smooth muscle cells (PASMCs). Additionally, role of cytohesin in this scenario is unknown in PASMCs. We, therefore, determined the involvement of Arf and cytohesin in U46619-induced stimulation of PLD in PASMCs, and the probable mechanism by which curcumin, a natural phenolic compound, inhibits the U46619 response. Treatment of PASMCs with U46619 stimulated PLD activity in the cell membrane, which was inhibited upon pretreatment with SQ29548 (Tp receptor antagonist), FIPI (PLD inhibitor), SecinH3 (inhibitor of cytohesins), and curcumin. Transfection of the cells with Tp, Arf-6, and cytohesin-1 siRNA inhibited U46619-induced activation of PLD. Upon treatment of the cells with U46619, Arf-6 and cytohesin-1 were translocated and associated in the cell membrane, which were not inhibited upon pretreatment of the cells with curcumin. Cytohesin-1 appeared to be necessary for in vitro binding of GTPγS with Arf-6; however, addition of curcumin inhibited binding of GTPγS with Arf-6 even in the presence of cytohesin-1. Our computational study suggests that although curcumin to some extent binds with Tp receptor, yet the inhibition of Arf6GDP to Arf6GTP conversion appeared to be an important mechanism by which curcumin inhibits U46619-induced increase in PLD activity in PASMCs.

Keywords

Phospholipase D Phosphatidic acid ADP ribosylation factor Cytohesin U46619 Smooth muscle cell Docking 

Abbreviations

HPASMC

Human pulmonary artery smooth muscle cells

PLD

Phospholipase D

Tp

TxA2 receptor

Arf

ADP ribosylation factor

GEF

Guanine nucleotide exchange factor

Notes

Acknowledgements

Financial assistance from Science and Engineering Research Board (SERB), Department of Science and Technology, Govt. of India is greatly acknowledged. Thanks are also due to late Dr. Tripti De (Scientist, CSIR-Indian Institute of Chemical Biology, Kolkata) for her interest in this work. Thanks are also due to the Bioinformatics Infrastructure Facility of the University of Kalyani for computational study.

References

  1. 1.
    Chakraborti S, Chowdhury A, Kar P, Das P, Shaikh S, Roy S, Chakraborti T (2009) Role of protein kinase C inNADPH oxidase derived \( {\text{O}}_{2}^{{ \cdot - }} \) mediated regulation of KV-LVOCC axis under U46619 induced increase in pulmonary artery smooth muscle cells. Arch Biochem Biophys 487:123–130CrossRefPubMedGoogle Scholar
  2. 2.
    EI-Azrez MA, Garceau V, Harbour D, Pivot-Pajot C, Bourgoin SG (2010) Cytohesin-1 regulates the Arf6-phospholipase D signalling axis in human neutrophils: impact on superoxide anion production and secretion. J Immunol 184:637–649CrossRefGoogle Scholar
  3. 3.
    Waite KA, Wallin R, Quallinotine MD, McPhail LC (1997) Phosphatidic acid-mediated phosphorylation of the NADPH oxidase component p47phox. Evidence that phosphatidic acid may activate a novel protein kinase. J Biol Chem 272:15569–15578CrossRefPubMedGoogle Scholar
  4. 4.
    Frohman MA (2015) The phospholipase D superfamily as therapeutic target. Trends Pharmacol 36:137–144CrossRefGoogle Scholar
  5. 5.
    Chakraborti S, Roy S, Mandal A, Dey K, Chowdhury A, Shaikh S, Chakraborti T (2012) Role of PKCα-p38MAPK-Giα axis in NADPH oxidase derived \( {\text{O}}_{2}^{{ \cdot - }} \) mediated activation of cPLA2 under U46619 stimulation in pulmonary artery smooth muscle cells. Arch Biochem Biophys 523:169–180CrossRefPubMedGoogle Scholar
  6. 6.
    Chakraborti T, Ghosh SK, Michael JR, Batabyal SK, Chakraborti S (1998) Targets of oxidative stress in cardiovascular system. Mol Cell Biochem 187:1–10CrossRefPubMedGoogle Scholar
  7. 7.
    Chakraborti T, Das S, Chakraborti S (2005) Proteolytic activation of protein kinase Cα in stimulating cPLA2 in pulmonary endothelium: involvement of a pertussis toxin sensitive protein. Biochemistry (USA) 44:5246–5247CrossRefGoogle Scholar
  8. 8.
    Wedgwood S, McMullan DM, Bekker JM, Fineman JR, Black SM (2001) Role of endothelin-1-induced superoxide and peroxynitrite production in rebound pulmonary hypertension associated with inhaled nitric oxide therapy. Cir Res 89:357–364CrossRefGoogle Scholar
  9. 9.
    Shome K, Nie Y, Romero G (1998) ADP ribosylation factor proteins mediate agonist-induced activation of phospholipase D. J Biol Chem 273:30836–30841CrossRefPubMedGoogle Scholar
  10. 10.
    Mitchell R, Robertson DN, Holland PJ, Collins D, Lutz EM, Johnson MS (2003) ADP ribosylation factor dependent phospholipase D activation by the M3 muscarinic receptor. J Biol Chem 278:33818–33830CrossRefPubMedGoogle Scholar
  11. 11.
    Massenburg D, Han JS, Liyanage M, Patton WA, Rhee SG, Moss J, Vaughan M (1994) Activation of rat brain phospholipase D by ADP ribosylation factors 1,5 and 6: separation of ADP ribosylation factor-dependent and oleate dependent enzymes. Proc natl Acad Sci (USA) 91:11718–11722CrossRefGoogle Scholar
  12. 12.
    Provost JJ, Fudge J, Israelit S, Siddiqi AR, Exton JH (1996) Tissue-specific distribution and subcellular distribution of phospholipase D in rat: evidence for distinct RhoA- and ADP-ribosylation factor (Arf) regulated isoenzymes. Biochem J 319:285–291CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Cockcroft S, Thomas GM, Fensome A, Geny B, Cunningham E, Gout I, Hiles I, Totty NF, Truong O, Hsuan JJ (1994) Phospholipase D: a downstream effector of ARF in granulocytes. Science 263:523–526CrossRefPubMedGoogle Scholar
  14. 14.
    Shome K, Vasudevan C, Romero G (1997) ARF proteins mediate insulin-dependent activation of phospholipase D. Curr Biol 7:387–396CrossRefPubMedGoogle Scholar
  15. 15.
    Robertson DN, Johnson MS, Moggach LO, Holland PJ, Lutz EM, Mitchell R (2003) Selective interaction of Arf1 with the carboxyl terminal tail domains of the 5HT2A receptor. Mol Pharmacol 64:1239–1250CrossRefPubMedGoogle Scholar
  16. 16.
    Li HS, Shome K, Rojas R, Rizzo MA, Vasudevan C, Fluharty E, Santy LC, Casanova JE, Romero G (2003) The guanine nucleotide exchange factor ARNO mediates the activation of Arf and phospholipase D by insulin. BMC Cell Biol 4:13CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Casanova JE (2007) Regulation of Arf activation: the sec7 family of guanine nucleotide exchange factors. Traffic 8:1476–1485CrossRefPubMedGoogle Scholar
  18. 18.
    Bourne HR, Sanders DA, McCormick F (1991) The GTPase superfamily: conserved structure and molecular mechanism. Nature 349:117–127CrossRefPubMedGoogle Scholar
  19. 19.
    Goldberg J (1998) Structural basis for activation of ARF GTPase: mechanisms of guanine nucleotide exchange and GTP–myristoyl switching. Cell 95:237–248CrossRefPubMedGoogle Scholar
  20. 20.
    Renault L, Guibert B, Cherfils J (2003) Structural snapshots of the mechanism and inhibition of a guanine nucleotide exchange factor. Nature 426:525–530CrossRefPubMedGoogle Scholar
  21. 21.
    Vetter IR, Wittinghofer A (2001) The guanine nucleotide-binding switch in three dimensions. Science 294:1299–1304CrossRefPubMedGoogle Scholar
  22. 22.
    Béraud-Dufour S, Paris S, Chabre M, Antonny B (1999) Dual interaction of ADP ribosylation factor 1 with Sec7 domain and with lipid membranes during catalysis of guanine nucleotide exchange. J Biol Chem 274:37629–37636CrossRefPubMedGoogle Scholar
  23. 23.
    Shome K, Rizzo MA, Vasudevan C, Andersen B, Romero G (2000) The activation of phospholipase D by endothelin-1, angiotensin II, and platelet-derived growth factor in vascular smooth muscle A10 cells is mediated by small G proteins of the ADP-ribosylation factor family. Endocrinol 141:2200–2208CrossRefGoogle Scholar
  24. 24.
    Jiang S, Han J, Li T, Xin Z, Ma Z, Di W, Hu W, Gong B, Di S, Wang D, Yang Y (2017) Curcumin as a potential protective compound against cardiac diseases. Pharmacol Res 119:373–383CrossRefPubMedGoogle Scholar
  25. 25.
    Kunnumakkara AB, Bordoloi D, Padmavathi G, Monisha J, Roy NK, Prasad S, Aggarwal BB (2016) Curcumin, the golden nutraceutical: multitargeting for multiple chronic diseases. Br J Pharmacol. doi: 10.1111/bph.13621 PubMedGoogle Scholar
  26. 26.
    Kruangtip O, Chootip K, Temkitthawon P, Changwichit K, Chuprajob T, Changtam C, Suksamrarn A, Khorana N, Scholfield CN, Ingkaninan K (2015) Curcumin analogues inhibit phosphodiesterase-5 and dilate rat pulmonary arteries. J Pharm Pharmacol 67:87–95CrossRefPubMedGoogle Scholar
  27. 27.
    Bronte E, Coppola G, Di Miceli R, Sucato V, Russo A, Novo S (2013) Role of curcumin in idiopathic pulmonary arterial hypertension treatment: a new therapeutic possibility. Med Hypotheses 81:923–926CrossRefPubMedGoogle Scholar
  28. 28.
    Peyroche A, Antonny B, Robineau S, Acker J, Cherfils J, Jackson CL (1999) Brefeldin A acts to stabilize an abortive ARF-GDP-Sec7 domain protein complex: involvement of specific residues of the Sec7 domain. Mol Cell 3:275–285CrossRefPubMedGoogle Scholar
  29. 29.
    Mansour SJ, Skaug J, Zhao XH, Giordano J, Scherer SW, Melancon P (1999) p200 ARF-GEP1: a golgi-localized guanine nucleotide exchange protein whose Sec7 domain is targeted by the drug brefeldin A. Proc natl Acad Sci (USA) 96:7968–7973CrossRefGoogle Scholar
  30. 30.
    Rümenapp U, Geiszt M, Wahn F, Schmidt M, Jakobs KH (1995) Evidence for ADP-Ribosylation-Factor-Mediated Activation of Phospholipase D by m3 Muscarinic Acetylcholine Receptor. Eur J Biochem 234:240–244CrossRefPubMedGoogle Scholar
  31. 31.
    Schmidt M, Hüwe SM, Fasselt B, Homann D, Rümenapp U, Sandmann J, Jakobs KH (1994) Mechanisms of phospholipase D stimulation by m3 muscarinic acetylcholine receptors. Evidence for involvement of tyrosine phosphorylation. Eur J Biochem 225:667–675CrossRefPubMedGoogle Scholar
  32. 32.
    Towbin H, Staehelin T, Gordon J (1979) Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci (USA) 76:4350–4354CrossRefGoogle Scholar
  33. 33.
    Franco M, Chardin P, Chabre M, Paris S (1996) Myristoylation-facilitated binding of the G protein ARF1 to membrane phospholipids is required for its activation by a soluble nucleotide exchange factor. J Biol Chem 271:1573–1578CrossRefPubMedGoogle Scholar
  34. 34.
    Caumont AS, Vitale N, Gensse M, Galas MC, Casanova JE, Bader MF (2000) Identification of a plasma membrane-associated guanine nucleotide exchange factor for ARF6 in chromaffin cells possible role in the regulated exocytotic pathway. J Biol Chem 275:15637–15644CrossRefPubMedGoogle Scholar
  35. 35.
    Smith PK, Krohn RI, Hermanson GT, Mallia AK, Gartner FH, Provenzaro MD, Fujimoto EK, Goeke NM, Olson BJ, Klenk DC (1985) Measurement of protein using bicinchoninic acid. Anal Biochem 150:76–85CrossRefPubMedGoogle Scholar
  36. 36.
    Webb B, Sali A (2014) Protein structure modeling with MODELLER. Protein Struct Predict 2014:1–5Google Scholar
  37. 37.
    Pierce BG, Wiehe K, Hwang H, Kim BH, Vreven T, Weng Z (2014) ZDOCK server: interactive docking prediction of protein–protein complexes and symmetric multimers. Bioinformatics 30:1771–1773CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Schneidman-Duhovny D, Inbar Y, Nussinov R, Wolfson HJ (2005) PatchDock and SymmDock: servers for rigid and symmetric docking. Nucl Acids Res 33:W363–W367CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Ramírez-Aportela E, López-Blanco JR, Chacón P (2016) FRODOCK 2.0: fast protein–protein docking server. Bioinformatics 32:2386–2388CrossRefPubMedGoogle Scholar
  40. 40.
    Zhang Y (2008) I-TASSER server for protein 3D structure prediction. BMC Bioinform 9:40CrossRefGoogle Scholar
  41. 41.
    Källberg M, Wang H, Wang S, Peng J, Wang Z, Lu H, Xu J (2012) Template-based protein structure modeling using the RaptorX web server. Nat Protoc 7:1511–1522CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Kelley LA, Mezulis S, Yates CM, Wass MN, Sternberg MJ (2015) The Phyre2 web portal for protein modeling, prediction and analysis. Nat Protoc 10:845–858CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Kim S, Thiessen PA, Bolton EE, Chen J, Fu G, Gindulyte A, Han L, He J, He S, Shoemaker BA, Wang J, Yu B, Zhang J, Bryant SH (2016) PubChem Substance and Compound databases. Nucl Acids Res 44:D1202–D1213CrossRefPubMedGoogle Scholar
  44. 44.
    Jones G, Willett P, Glen RC, Leach AR, Taylor R (1997) Development and validation of a genetic algorithm for flexible docking. J Mol Biol 267:727–748CrossRefPubMedGoogle Scholar
  45. 45.
    David WW (1978) Biostatistics: a foundation for analysis in health sciences. Wiley, New York, p 219Google Scholar
  46. 46.
    Lai X, Ye L, Liao Y, Jin L, Ma Q, Lu B, Sun Y, Shi Y, Zhou N (2016) Agonist-induced activation of histamine H3 receptor signals to extracellular signal-regulated kinases 1 and 2 through PKC-, PLD-, and EGFR-dependent mechanisms. J Neurochem 137:200–215CrossRefPubMedGoogle Scholar
  47. 47.
    Béraud-Dufour S, Robineau S, Chardin P, Paris S, Chabre M, Cherfils J, Antonny B (1998) A glutamic finger in the guanine nucleotide exchange factor ARNO displaces Mg2+ and the beta-phosphate to destabilize GDP on ARF1. EMBO J 17:3651–3659CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Ohguchi K, Kasai T, Nozawa Y (1997) Tyrosine phosphorylation of 100-115 kDa proteins by phosphatidic acid generated via phospholipase D activation in HL60 granulocytes. Biochim Biophys Acta 1346:301–304CrossRefPubMedGoogle Scholar
  49. 49.
    Tsai MH, Yu CL, Wei FS, Stacey DW (1989) The effect of GTPase activating protein upon ras is inhibited by mitogenically responsive lipids. Science 243:522–526CrossRefPubMedGoogle Scholar
  50. 50.
    Cavenagh MM, Whitney JA, Carroll K, Cj Zhang, Boman AL, Rosenwald AG, Mellman I, Kahn RA (1996) Intracellular distribution of Arf proteins in mammalian cells. Arf6 is uniquely localized to the plasma membrane. J Biol Chem 271:21767–21774CrossRefPubMedGoogle Scholar
  51. 51.
    Meacci E, Tsai SC, Adamik R, Moss J, Vaughan M (1997) Cytohesin-1, a cytosolic guanine nucleotide exchange protein for ADP ribosylation factor. Proc natl Acad Sci (USA) 94:1745–1748CrossRefGoogle Scholar
  52. 52.
    D’Souza-Schorey C, Li G, Colombo MI, Stahl PD (1995) A regulatory role for ARF6 in receptor-mediated endocytosis. Science 267:1175–1178CrossRefPubMedGoogle Scholar
  53. 53.
    Kolev TM, Velcheva EA, Stamboliyska BA, Spiteller M (2005) DFT and experimental studies of the structure and vibrational spectra of curcumin. Int J Quantum Chem 102:1069–1079CrossRefGoogle Scholar
  54. 54.
    Aggarwal BB, Kumar A, Bharti AC (2003) Anticancer potential of curcumin: preclinical and clinical studies. Anticancer Res 23:363–398PubMedGoogle Scholar
  55. 55.
    Goel A, Kunnumakkara AB, Aggarwal BB (2008) Curcumin as “Curecumin”: from kitchen to clinic. Biochem Pharmacol 75:787–809CrossRefPubMedGoogle Scholar
  56. 56.
    Archer S, Rich S (2000) Primary pulmonary hypertension: a vascular biology and translational research “Work in progress”. Circulation 102:2781–2791CrossRefPubMedGoogle Scholar
  57. 57.
    Azuma Y, Kosaka K, Kashimata M (2007) Phospholipase D-dependent and –independent p38MAPK activation pathways are required for superoxide production and chemotactic induction, respectively, in rat neutrophils stimulated by fMLP. Eur J Pharmacol 568:260–268CrossRefPubMedGoogle Scholar
  58. 58.
    Peng JJ, Liu B, Xu JY, Peng J, Luo XJ (2017) NADPH oxidase: its potential role in promotion of pulmonary arterial hypertension. Naunyn Schmiedebergs Arch Pharmacol 390:331–338CrossRefPubMedGoogle Scholar
  59. 59.
    Hood KY, Montezano AC, Harvey AP, Nilsen M, MacLean MR, Touyz RM (2016) Nicotinamide adenine dinucleotide phosphate oxidase-mediated redox signaling and vascular remodeling by 16α-Hydroxyestrone in human pulmonary artery cells: implications in pulmonary arterial hypertension. Hypertension 68:796–808CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    Tate RM, Venthuysen KM, Shasby DM, Mc- Murtry IF, Repine JE (1982) Oxygen radical mediated permeability edema and vasoconstriction in isolated perfused rabbit lungs. Am Reu Respir Dis 126:802–806Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Sajal Chakraborti
    • 1
    Email author
  • Jaganmay Sarkar
    • 1
  • Rajabrata Bhuyan
    • 1
  • Tapati Chakraborti
    • 1
  1. 1.Department of Biochemistry and BiophysicsUniversity of KalyaniKalyaniIndia

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