Skip to main content
SpringerLink
Log in

TRPM2 Channel Regulates Endothelial Barrier Function

  • Conference paper
  • First Online:
Book cover Membrane Receptors, Channels and Transporters in Pulmonary Circulation

Part of the book series: Advances in Experimental Medicine and Biology ((volume 661))

Abstract

Oxidative [Au1]stress, through the production of oxygen metabolites such as hydrogen peroxide[Au2] (H2O2), increases vascular endothelial permeability and plays a crucial role in several lung diseases. The transient receptor potential (melastatin) 2 (TRPM2) is an oxidant-sensitive, nonselective cation channel that is widely expressed in mammalian tissues, including the vascular endothelium. We have demonstrated the involvement of TRPM2 in mediating oxidant-induced calcium entry and endothelial hyperpermeability in cultured pulmonary artery endothelial cells. Here, we provide evidence that neutrophil activation-dependent increase in endothelial permeability and neutrophil extravasation requires TRPM2 in cultured endothelial cells. In addition, protein kinase Cα (PKCα) that rapidly colocalizes with the short (nonconducting) TRPM2 isoform after exposure to hydrogen peroxide positively regulates calcium entry through the functional TRPM2 channel. Thus, increase in lung microvessel permeability and neutrophil sequestration depends on the activation of endothelial TRPM2 by neutrophilic oxidants and on PKCα regulation of TRPM2 channel activity. Manipulating TRPM2 function in the endothelium may represent a novel strategy aimed to prevent oxidative stress-related vascular dysfunction.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 189.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 249.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 329.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Johnson A, Phillips P, Hocking D, Tsan MF, Ferro T (1989) Protein kinase C inhibitor prevents pulmonary edema in response to H2O2. Am J Physiol Heart Circ Physiol 256:H1012-H1022

    CAS  Google Scholar 

  2. Stevens T, Garcia JG, Shasby DM, Bhattacharya J, Malik AB (2000) Mechanisms regulating endothelial cell barrier function. Am J Physiol Lung Cell Mol Physiol 279:L419-L422

    PubMed  CAS  Google Scholar 

  3. Barnard ML, Matalon S (1992) Mechanisms of extracellular reactive oxygen species injury to the pulmonary microvasculature. J Appl Physiol 72:1724-1729

    PubMed  CAS  Google Scholar 

  4. Lum H, Roebuck K (2001) Oxidant stress and endothelial cell dysfunction. Am J Physiol Cell Physiol 280:C719-C741

    PubMed  CAS  Google Scholar 

  5. Siflinger-Birnboim A, Goligorsky MS, Delvecchio PJ, Malik AB (1992) Activation of protein kinase C pathway contributes to hydrogen peroxide-induced increase in endothelial permeability. Lab Invest 67:24-30

    PubMed  CAS  Google Scholar 

  6. Dreher D, Junod AF (1995) Differential effects of superoxide, hydrogen peroxide, and hydroxyl radical on intracellular calcium in human endothelial cells. J Cell Physiol 162:147-153

    Article  PubMed  CAS  Google Scholar 

  7. Volk T, Hensel M, Kox WJ (1997) Transient Ca2+ changes in endothelial cells induced by low doses of reactive oxygen species: role of hydrogen peroxide. Mol Cell Biochem 171:11-21

    Article  PubMed  CAS  Google Scholar 

  8. Groschner K, Rosker C, Lukas M (2004) Role of TRP channels in oxidative stress. Novartis Found Symp 258:222-230

    Article  PubMed  CAS  Google Scholar 

  9. Kwan HY, Huang Y, Yao X (2007) TRP channels in endothelial function and dysfunction. Biochim Biophys Acta 1772:907-914

    Article  PubMed  CAS  Google Scholar 

  10. Dietrich A, Gudermann T (2008) Another TRP to endothelial dysfunction: TRPM2 and endothelial permeability. Circ Res 102:275-277

    Article  PubMed  CAS  Google Scholar 

  11. Hecquet CM, Ahmmed GU, Vogel SM, Malik AB (2008) Role of TRPM2 channel in mediating H2O2-induced Ca2+ entry and endothelial hyperpermeability. Circ Res 102:347-355

    Article  PubMed  CAS  Google Scholar 

  12. Sano Y, Inamura K, Miyake A et al (2001) Immunocyte Ca2+ influx system mediated by LTRPC2. Science 293:1327-1330

    Article  PubMed  CAS  Google Scholar 

  13. Fonfria E, Marshall IC, Benham CD et al (2004) TRPM2 channel opening in response to oxidative stress is dependent on activation of poly(ADP-ribose) polymerase. Br J Pharmacol 143:186-192

    Article  PubMed  CAS  Google Scholar 

  14. Perraud AL, Takanishi CL, Shen B et al (2005) Accumulation of free ADP-ribose from mitochondria mediates oxidative stress-induced gating of TRPM2 cation channels. J Biol Chem 280:6138-6148

    Article  PubMed  CAS  Google Scholar 

  15. Kraft R, Grimm C, Grosse K et al (2004) Hydrogen peroxide and ADP-ribose induce TRPM2-mediated calcium influx and cation currents in microglia. Am J Physiol 286:C129-C137

    Article  CAS  Google Scholar 

  16. Heiner I, Eisfeld J, Luckhoff A (2003) Role and regulation of TRP channels in neutrophil granulocytes. Cell Calcium 33:533-540

    Article  PubMed  CAS  Google Scholar 

  17. Kolisek M, Beck A, Fleig A, Penner R (2005) Cyclic ADP-ribose and hydrogen peroxide synergize with ADP-ribose in the activation of TRPM2 channels. Mol Cell 18:61-69

    Article  PubMed  CAS  Google Scholar 

  18. Kühn FJ, Heiner I, Luckhoff A (2005) TRPM2: a calcium influx pathway regulated by oxidative stress and the novel second messenger ADP-ribose. Pflügers Arch 451:212-219

    Article  PubMed  Google Scholar 

  19. Maruyama Y, Ogura T, Mio K et al (2007) Three-dimensional reconstruction using transmission electron microscopy reveals a swollen, bell-shaped structure of transient receptor potential melastatin type 2 cation channel. J Biol Chem 282:36961-36970

    Article  PubMed  CAS  Google Scholar 

  20. Zhang W, Chu X, Tong Q, Cheung JY, Conrad K, Masker K, Miller BA (2003) A novel TRPM2 isoform inhibits calcium influx and susceptibility to cell death. J Biol Chem 278:16222-16229

    Article  PubMed  CAS  Google Scholar 

  21. Wysolmerski RB, Lagunoff D (1991) Regulation of permeabilized endothelial cell retraction by myosin phosphorylation. Am J Physiol 261:C32-C40

    PubMed  CAS  Google Scholar 

  22. Tiruppathi C, Freichel M, Vogel SM et al (2002) Impairment of store-operated Ca2+ entry in TRPC4-/- mice interferes with increase in lung microvascular permeability. Circ Res 91:70-76

    Article  PubMed  CAS  Google Scholar 

  23. Paria BC, Vogel SM, Ahmmed GU et al (2004) Tumor necrosis factor-alpha-induced TRPC1 expression amplifies store-operated Ca2+ influx and endothelial permeability. Am J Physiol 287:L1303-L1313

    CAS  Google Scholar 

  24. Singh I, Knezevic N, Ahmmed GU, Kini V, Malik AB, Mehta D (2002) Gαq-TRPC6-mediated Ca2+ entry induces RhoA activation and resultant endothelial cell shape change in response to thrombin. J Biol Chem 282:7833-7843

    Article  Google Scholar 

  25. Paria BC, Bair AM, Xue J, Yu Y, Malik AB, Tiruppathi C (2006) Ca2+ influx induced by protease-activated receptor-1 activates a feed-forward mechanism of TRPC1 expression via nuclear factor-κB activation in endothelial cells. J Biol Chem 281:20715-20727

    Article  PubMed  CAS  Google Scholar 

  26. Mehta D, Ahmmed GU, Paria BC et al (2003) RhoA interaction with inositol 1,4,5-trisphosphate receptor and transient receptor potential channel-1 regulates Ca2+ entry. Role in signaling increased endothelial permeability. J Biol Chem 278:33492-33500

    Article  PubMed  CAS  Google Scholar 

  27. Cioffi DL, Stevens T (2006) Regulation of endothelial cell barrier function by store-operated calcium entry. Microcirculation 13:709-723

    Article  PubMed  CAS  Google Scholar 

  28. Balzer M, Lintschinger B, Groschner K (1999) Evidence for a role of Trp proteins in the oxidative stress-induced membrane conductances of porcine aortic endothelial cells. Cardiovasc Res 42:543-549

    Article  PubMed  CAS  Google Scholar 

  29. Poteser M, Graziani A, Rosker C et al (2006) TRPC3 and TRPC4 associate to form a redox-sensitive cation channel. Evidence for expression of native TRPC3-TRPC4 heterometric channels in endothelial cells. J Biol Chem 281:13588-13595

    Article  PubMed  CAS  Google Scholar 

  30. Kaslovsky RA, Parker K, Siflinger-Birnboim A, Malik AB (1995) Increased endothelial permeability after neutrophil activation occurs by a diffusion-dependent mechanism. Microvasc Res 49:227-232

    Article  PubMed  CAS  Google Scholar 

  31. Wang Q, Doerschuk CM (2000) Neutrophil-induced changes in the biomechanical properties of endothelial cells: roles of ICAM-1 and reactive oxygen species. J Immunol 164:6487-6494

    PubMed  CAS  Google Scholar 

  32. Siflinger-Birnboim A, Malik AB (1996) Regulation of endothelial permeability by second messengers. New Horiz 4:87-98

    PubMed  CAS  Google Scholar 

  33. Yamamoto S, Shimizu S, Kiyonaka S et al (2008) TRPM2-mediated Ca2+ influx induces chemokine production in monocytes that aggravates inflammatory neutrophil infiltration. Nat Med 14:738-747

    Article  PubMed  CAS  Google Scholar 

  34. Han XB, Liu X, Hsueh W, De Plaen IG (2004) Macrophage inflammatory protein-2 mediates the bowel injury induced by platelet-activating factor. Am J Physiol Gastrointest Liver Physiol 287:G1220-G1226

    Article  PubMed  CAS  Google Scholar 

  35. Buanne P, Di Carlo E, Caputi L et al (2007) Crucial pathophysiological role of CXCR2 in experimental ulcerative colitis in mice. J Leukoc Biol 82:1239-1246

    Article  PubMed  CAS  Google Scholar 

  36. Zhang W, Tong Q, Conrad K, Wozney J, Cheung JY, Miller BA (2007) Regulation of TRP channel TRPM2 by the tyrosine phosphatase PTPL1. Am J Physiol Cell Physiol 292:C1746-C1758

    Article  PubMed  CAS  Google Scholar 

  37. Gopalakrishna R, Anderson WB (1989) Ca2+- and phospholipid-independent activation of protein kinase C by selective oxidative modification of the regulatory domain. Proc Natl Acad Sci U S A 86:6758-6762

    Article  PubMed  CAS  Google Scholar 

  38. Gopalakrishna R, Jaken S (2000) Protein kinase C signaling and oxidative stress. Free Rad Biol Med 28:1349-1361

    Article  PubMed  CAS  Google Scholar 

  39. Nathan CF (1987) Neutrophil activation on biological surfaces. Massive secretion of hydrogen peroxide in response to products of macrophages and lymphocytes. J Clin Invest 80:1550-1560

    Article  PubMed  CAS  Google Scholar 

  40. Tong Q, Zhang W, Conrad K et al (2006) Regulation of the transient receptor potential channel TRPM2 by the Ca2+ sensor calmodulin. J Biol Chem 281:9076-9085

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmacology and Center for Lung and Vascular Biology, University of Illinois College of Medicine, Chicago, IL, 60612, USA

    Claudie M. Hecquet, Gias U. Ahmmed & Asrar B. Malik

Authors
  1. Claudie M. Hecquet
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gias U. Ahmmed
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Asrar B. Malik
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Claudie M. Hecquet .

Editor information

Editors and Affiliations

  1. Departments of Medicine and Pharmacology, University of Illinois at Chicago, Chicago, 60612, USA

    Jason X. -J. Yuan

  2. Guy’s Hospital Campus, Dept. Physiology, King’s College London, London, SE1 1UL, United Kingdom

    Jeremy P. T. Ward

Rights and permissions

Reprints and permissions

Copyright information

© 2010 Humana Press, a part of Springer Science+Business Media, LLC

About this paper

Cite this paper

Hecquet, C.M., Ahmmed, G.U., Malik, A.B. (2010). TRPM2 Channel Regulates Endothelial Barrier Function. In: Yuan, JJ., Ward, J. (eds) Membrane Receptors, Channels and Transporters in Pulmonary Circulation. Advances in Experimental Medicine and Biology, vol 661. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60761-500-2_10

Download citation

Publish with us

Policies and ethics

Search

Navigation