The Journal of Membrane Biology

, Volume 209, Issue 1, pp 31–41

The Role of TRP Channels in Oxidative Stress-induced Cell Death

Article

Abstract

The transient receptor potential (TRP) protein superfamily is a diverse group of voltage-independent calcium-permeable cation channels expressed in mammalian cells. These channels have been divided into six subfamilies, and two of them, TRPC and TRPM, have members that are widely expressed and activated by oxidative stress. TRPC3 and TRPC4 are activated by oxidants, which induce Na+ and Ca2+ entry into cells through mechanisms that are dependent on phospholipase C. TRPM2 is activated by oxidative stress or TNFα, and the mechanism involves production of ADP-ribose, which binds to an ADP-ribose binding cleft in the TRPM2 C-terminus. Treatment of HEK 293T cells expressing TRPM2 with H2O2 resulted in Ca2+ influx and increased susceptibility to cell death, whereas coexpression of the dominant negative isoform TRPM2-S suppressed H2O2-induced Ca2+ influx, the increase in [Ca2+]i, and onset of apoptosis. U937-ecoR monocytic cells expressing increased levels of TRPM2 also exhibited significantly increased [Ca2+]i and increased apoptosis after treatment with H2O2 or TNFα. A dramatic increase in caspase 8, 9, 3, 7, and PARP cleavage was observed in TRPM2-expressing cells, demonstrating a downstream mechanism through which cell death is mediated. Inhibition of endogenous TRPM2 function through three approaches, depletion of TRPM2 by RNA interference, blockade of the increase in [Ca2+]i through TRPM2 by calcium chelation, or expression of the dominant negative splice variant TRPM2-S protected cell viability. H2O2 and amyloid β-peptide also induced cell death in primary cultures of rat striatal cells, which endogenously express TRPM2. TRPM7 is activated by reactive oxygen species/nitrogen species, resulting in cation conductance and anoxic neuronal cell death, which is rescued by suppression of TRPM7 expression. TRPM2 and TRPM7 channels are physiologically important in oxidative stress-induced cell death.

Keywords

Apoptosis Intracellular Ca2+ Oxidative stress TRPC3 TRPM2 TRPM7 

References

  1. Aarts M., Iihara K., Wei W.L., Xiong Z.G., Arundine M., Cerwinski W., MacDonald J.F., Tymianski M. 2003. A key role for TRPM7 channels in anoxic neuronal death. Cell 115:863–877CrossRefPubMedGoogle Scholar
  2. Agam K., von Campenhausen M., Levy S., Ben-Ami H.C., Cook B., Kirschfeld K., Minke B. 2000. Metabolic stress reversibly activates the Drosophila light-sensitive channels TRP and TRPL in vivo. J. Neurosci. 20:5748–5755PubMedGoogle Scholar
  3. 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. 42:543–549CrossRefPubMedGoogle Scholar
  4. Bauer M.K., Vogt M., Los M., Siegel J., Wesselborg S., Schulze-Osthoff K. 1998. Role of reactive oxygen intermediates in activation-induced CD95 (APO-1/Fas) ligand expression. J. Biol. Chem. 273:8048–8055CrossRefPubMedGoogle Scholar
  5. Bezzerides V.J., Ramsey I.S., Kotecha S., Greka A., Clapham D.E. 2004. Rapid vesicular translocation and insertion of TRP channels. Nat. Cell. Biol. 6:709–720CrossRefPubMedGoogle Scholar
  6. Boulay G., Brown D.M., Qin N., Jiang M., Dietrich A., Zhu M.X., Chen Z., Birnbaumer M., Mikoshiba K., Birnbaumer L. 1999. Modulation of Ca2+ entry by polypeptides of the inositol 1,4, 5-trisphosphate receptor (IP3R) that bind transient receptor potential (TRP): evidence for roles of TRP and IP3R in store depletion-activated Ca(2+) entry. Proc. Natl. Acad. Sci. USA 96:14955–14960CrossRefPubMedGoogle Scholar
  7. Buniel M.C., Schilling W.P., Kunze D.L. 2003. Distribution of transient receptor potential channels in the rat carotid chemosensory pathway. J. Comp. Neurol. 464:404–413CrossRefPubMedGoogle Scholar
  8. Butterfield D.A. 2003. Amyloid beta-peptide [1-42]-associated free radical-induced oxidative stress and neurodegeneration in Alzheimer’s disease brain: mechanisms and consequences. Curr Med Chem 10:2651–2659CrossRefPubMedGoogle Scholar
  9. Cabaner C., Gajate C., Macho A., Munoz E., Modolell M., Mollinedo F. 1999. Induction of apoptosis in human mitogen-activated peripheral blood T-lymphocytes by the ether phospholipid ET-18-OCH3: involvement of the Fas receptor/ligand system. Br. J. Pharmacol. 127:813–825CrossRefPubMedGoogle Scholar
  10. Chakraborti T., Das S., Mondal M., Roychoudhury S., Chakraborti S. 1999. Oxidant, mitochondria and calcium: an overview. Cell Signal 11:77–85CrossRefPubMedGoogle Scholar
  11. Chandra J., Samali A., Orrenius S. 2000. Triggering and modulation of apoptosis by oxidative stress. Free Radic. Biol. Med. 29:323–333CrossRefPubMedGoogle Scholar
  12. Clapham D.E. 2003. TRP channels as cellular sensors. Nature 426:517–524CrossRefPubMedGoogle Scholar
  13. Crompton M. 1999. The mitochondrial permeability transition pore and its role in cell death. Biochem. J. 341:233–249CrossRefPubMedGoogle Scholar
  14. Davidovic L., Vodenicharov M., Affar E.B., Poirier G.G. 2001. Importance of poly(ADP-ribose) glycohydrolase in the control of poly(ADP-ribose) metabolism. Exp. Cell Res. 268:7–13CrossRefPubMedGoogle Scholar
  15. Denning T.L., Takaishi H., Crowe S.E., Boldogh I., Jevnikar A., Ernst P.B. 2002. Oxidative stress induces the expression of Fas and Fas ligand and apoptosis in murine intestinal epithelial cells. Free Radic. Biol. Med. 33:1641–1650CrossRefPubMedGoogle Scholar
  16. Duncan L.M., Deeds J., Hunter J., Shao J., Holmgren L.M., Woolf E.A., Tepper R.I., Shyjan A.W. 1998. Down-regulation of the novel gene melastatin correlates with potential for melanoma metastasis. Cancer. Res. 58:1515–1520PubMedGoogle Scholar
  17. Ermak G., Davies K.J. 2002. Calcium and oxidative stress: from cell signaling to cell death. Mol. Immunol. 38:713–721CrossRefPubMedGoogle Scholar
  18. Fonfria E., Marshall I.C., Boyfield I., Skaper S.D., Hughes J.P., Owen D.E., Zhang W., Miller B.A., Benham C.D., McNulty S. 2005. Amyloid beta-peptide(1-42) and hydrogen peroxide-induced toxicity are mediated by TRPM2 in rat primary striatal cultures. J. Neurochem. 95: 715–722.CrossRefPubMedGoogle Scholar
  19. Fonfria E., Marshall I.C.B., Benham C.D., Boyfield I., Brown J.D., Hill K., Hughes J.P., Skaper S.D., Scharenberg A.M., McNulty S. 2004. TRPM2 Channel Opening in Response to Oxidative Stress is Dependent on Activation of Poly (ADP-Ribose) Polymerase. Br.J. Pharmacol. 143:186–192CrossRefPubMedGoogle Scholar
  20. Goel M., Sinkins W.G., Schilling W.P. 2002. Selective association of TRPC channel subunits in rat brain synaptosomes. J. Biol. Chem. 277:48303–48310CrossRefPubMedGoogle Scholar
  21. Gopalakrishna R., Jaken S. 2000. Protein kinase C signaling and oxidative stress. Free Radic. Biol. Med. 28:1349–1361CrossRefPubMedGoogle Scholar
  22. Green D.R., Kroemer G. 2004. The pathophysiology of mitochondrial cell death. Science 305:626–629CrossRefPubMedGoogle Scholar
  23. Groschner K., Rosker C., Lukas M. 2004. Role of TRP channels in oxidative stress. Novartis Found. Symp. 258:222–230; discussion 231–235, 263–266PubMedCrossRefGoogle Scholar
  24. Halestrap A.P., McStay G.P., Clarke S.J. 2002. The permeability transition pore complex: another view. Biochimie 84:153–166CrossRefPubMedGoogle Scholar
  25. Han W.K., Sapirstein A., Hung C.C., Alessandrini A., Bonventre J.V. 2003. Cross-talk between cytosolic phospholipase A2 alpha (cPLA2 alpha) and secretory phospholipase A2 (sPLA2) in hydrogen peroxide-induced arachidonic acid release in murine mesangial cells: sPLA2 regulates cPLA2 alpha activity that is responsible for arachidonic acid release. J. Biol. Chem. 278:24153–24163CrossRefPubMedGoogle Scholar
  26. Hanano T., Hara Y., Shi J., Morita H., Umebayashi C., Mori E., Sumimoto H., Ito Y., Mori Y., Inoue R. 2004. Involvement of TRPM7 in cell growth as a spontaneously activated Ca2+ entry pathway in human retinoblastoma cells. J. Pharmacol. Sci. 95:403–419CrossRefPubMedGoogle Scholar
  27. Hara Y., Wakamori M., Ishii M., Maeno E., Nishida M., Yoshida T., Yamada H., Shimizu S., Mori E., Kudoh J., Shimizu N., Kurose H., Okada Y., Imoto K., Mori Y. 2002. LTRPC2 Ca2+-permeable channel activated by changes in redox status confers susceptibility to cell death. Mol. Cell. 9:163–173CrossRefPubMedGoogle Scholar
  28. Hardie R.C., Minke B. 1992. The trp gene is essential for a light-activated Ca2+ channel in Drosophila photoreceptors. Neuron 8:643–651CrossRefPubMedGoogle Scholar
  29. Harteneck C., Plant T.D., Schultz G. 2000. From worm to man: three subfamilies of TRP channels. Trends Neurosci 23:159–166CrossRefPubMedGoogle Scholar
  30. He Y., Yao G., Savoia C., Touyz R.M. 2005. Transient receptor potential melastatin 7 ion channels regulate magnesium homeostasis in vascular smooth muscle cells: role of angiotensin II. Circ. Res. 96:207–215CrossRefPubMedGoogle Scholar
  31. Heiner I., Eisfeld J., Halaszovich C.R., Wehage E., Jungling E., Zitt C., Luckhoff A. 2003a. Expression profile of the transient receptor potential (TRP) family in neutrophil granulocytes: evidence for currents through long TRP channel 2 induced by ADP-ribose and NAD. Biochem. J. 371:1045–1053CrossRefGoogle Scholar
  32. Heiner I., Eisfeld J., Luckhoff A. 2003b. Role and regulation of TRP channels in neutrophil granulocytes. Cell. Calcium. 33:533–540CrossRefGoogle Scholar
  33. Herson P.S., Lee K., Pinnock R.D., Hughes J., Ashford M.L. 1999. Hydrogen peroxide induces intracellular calcium overload by activation of a non-selective cation channel in an insulin-secreting cell line. J. Biol. Chem. 274:833–841CrossRefPubMedGoogle Scholar
  34. Hofmann T., Obukhov A.G., Schaefer M., Harteneck C., Gudermann T., Schultz G. 1999. Direct activation of human TRPC6 and TRPC3 channels by diacylglycerol. Nature 397:259–263CrossRefPubMedGoogle Scholar
  35. Hofmann T., Schaefer M., Schultz G., Gudermann T. 2002. Subunit composition of mammalian transient receptor potential channels in living cells. Proc. Natl. Acad. Sci. USA 99:7461–7467CrossRefPubMedGoogle Scholar
  36. Jo D.G., Jun J.I., Chang J.W., Hong Y.M., Song S., Cho D.H., Shim S.M., Lee H.J., Cho C., Kim do H., Jung Y.K. 2004. Calcium binding of ARC mediates regulation of caspase 8 and cell death. Mol. Cell. Biol. 24:9763–9770CrossRefPubMedGoogle Scholar
  37. Jones B.E., Lo C.R., Liu H., Pradhan Z., Garcia L., Srinivasan A., Valentino K.L., Czaja M.J. 2000. Role of caspases and NF-kappaB signaling in hydrogen peroxide- and superoxide-induced hepatocyte apoptosis. Am. J. Physiol. 278:G693–G699Google Scholar
  38. Klohn P.C., Soriano M.E., Irwin W., Penzo D., Scorrano L., Bitsch A., Neumann H.G., Bernardi P. 2003. Early resistance to cell death and to onset of the mitochondrial permeability transition during hepatocarcinogenesis with 2-acetylaminofluorene. Proc. Natl. Acad. Sci. USA 100:10014–10019CrossRefPubMedGoogle Scholar
  39. 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. 18:61–69CrossRefPubMedGoogle Scholar
  40. Kozak J.A., Cahalan M.D. 2003. MIC channels are inhibited by internal divalent cations but not ATP. Biophys. J. 84:922–927PubMedCrossRefGoogle Scholar
  41. Kraft R., Grimm C., Grosse K., Hoffmann A., Sauerbruch S., Kettenmann H., Schultz G., Harteneck C. 2004. Hydrogen peroxide and ADP-ribose induce TRPM2-mediated calcium influx and cation currents in microglia. Am. J. Physiol. 286:C129–137CrossRefGoogle Scholar
  42. Kuhn F.J., Luckhoff A. 2004. Sites of the NUDT9-H domain critical for ADP-ribose activation of the cation channel TRPM2. J. Biol. Chem. 279:46431–4647CrossRefPubMedGoogle Scholar
  43. Langley B., Ratan R.R. 2004. Oxidative stress-induced death in the nervous system: cell cycle dependent or independent? J. Neurosci. Res 77:621–9CrossRefGoogle Scholar
  44. Leslie C.C. 1997. Properties and regulation of cytosolic phospholipase A2. J. Biol. Chem. 272:16709–16712CrossRefPubMedGoogle Scholar
  45. Li H.S., Montell C. 2000. TRP and the PDZ protein, INAD, form the core complex required for retention of the signalplex in Drosophila photoreceptor cells. J Cell Biol 150:1411–1422CrossRefPubMedGoogle Scholar
  46. Lintschinger B., Balzer-Geldsetzer M., Baskaran T., Graier W.F., Romanin C., Zhu M.X., Groschner K. 2000. Coassembly of Trp1 and Trp3 proteins generates diacylglycerol- and Ca2+-sensitive cation channels. J. Biol. Chem. 275:27799–27805PubMedGoogle Scholar
  47. Lipton P. 1999. Ischemic cell death in brain neurons. Physiol Rev 79:1431–1568PubMedGoogle Scholar
  48. Lockwich T.P., Liu X., Singh B.B., Jadlowiec J., Weiland S., Ambudkar I.S. 2000. Assembly of Trp1 in a signaling complex associated with caveolin-scaffolding lipid raft domains. J. Biol. Chem. 275:11934–42CrossRefPubMedGoogle Scholar
  49. Ma S., Ochi H., Cui L., Zhang J., He W. 2003. Hydrogen peroxide induced down-regulation of CD28 expression of Jurkat cells is associated with a change of site alpha-specific nuclear factor binding activity and the activation of caspase-3. Exp Gerontol. 38:1109–1118CrossRefPubMedGoogle Scholar
  50. Matsura T., Kai M., Fujii Y., Ito H., Yamada K. 1999. Hydrogen peroxide-induced apoptosis in HL-60 cells requires caspase-3 activation. Free Radic Res 30:73–83PubMedGoogle Scholar
  51. Matsushita M., Kozak J.A., Shimizu Y., McLachlin D.T., Yamaguchi H., Wei F.Y., Tomizawa K., Matsui H., Chait B.T., Cahalan M.D., Nairn A.C. 2005. Channel function is dissociated from the intrinsic kinase activity and autophosphorylation of TRPM7/ChaK1. J. Biol. Chem. 280:20793–20803CrossRefPubMedGoogle Scholar
  52. McHugh D., Flemming R., Xu S.Z., Perraud A.L., Beech D.J. 2003. Critical intracellular Ca2+ dependence of transient receptor potential melastatin 2 (TRPM2) cation channel activation. J. Biol. Chem. 278:11002–11006CrossRefPubMedGoogle Scholar
  53. McNulty S., Fonfria E. 2005. The role of TRPM channels in cell death. Pfluegers. Arch. 451:235–242CrossRefGoogle Scholar
  54. Minke B., Cook B. 2002. TRP channel proteins and signal transduction. Physiol. Rev. 82:429–472PubMedGoogle Scholar
  55. Montell C., 2001. Physiology, phylogeny, and functions of the TRP superfamily of cation channels. Sci STKE 2001:RE1Google Scholar
  56. Montell C. 2003. Mg2+ homeostasis: the Mg2+nificent TRPM chanzymes. Curr. Biol. 13:R799–R801CrossRefPubMedGoogle Scholar
  57. Montell, C. 2005. The TRP superfamily of cation channels. Sci STKE 2005:re3Google Scholar
  58. Montell C., Rubin G.M. 1989. Molecular characterization of the Drosophila trp locus: a putative integral membrane protein required for phototransduction. Neuron 2:1313–1323CrossRefPubMedGoogle Scholar
  59. Nadler M.J., Hermosura M.C., Inabe K., Perraud A.L., Zhu Q., Stokes A.J., Kurosaki T., Kinet J.P., Penner R., Scharenberg A.M., Fleig A. 2001. LTRPC7 is a Mg.ATP-regulated divalent cation channel required for cell viability. Nature 411:590–595CrossRefPubMedGoogle Scholar
  60. Nagamine K., Kudoh J., Minoshima S., Kawasaki K., Asakawa S., Ito F., Shimizu N. 1998. Molecular cloning of a novel putative Ca2+ channel protein (TRPC7) highly expressed in brain. Genomics 54:124–131CrossRefPubMedGoogle Scholar
  61. Orrenius S., Zhivotovsky B., Nicotera P. 2003. Regulation of cell death: the calcium-apoptosis link. Nat. Rev. Mol. Cell. Biol. 4:552–565CrossRefPubMedGoogle Scholar
  62. Partida-Sanchez S., Cockayne D.A., Monard S., Jacobson E.L., Oppenheimer N., Garvy B., Kusser K., Goodrich S., Howard M., Harmsen A., Randall T.D., Lund F.E. 2001. Cyclic ADP-ribose production by CD38 regulates intracellular calcium release, extracellular calcium influx and chemotaxis in neutrophils and is required for bacterial clearance in vivo. Nat Med 7:1209–1216CrossRefPubMedGoogle Scholar
  63. Perraud A.L., Fleig A., Dunn C.A., Bagley L.A., Launay P., Schmitz C., Stokes A.J., Zhu Q., Bessman M.J., Penner R., Kinet J.P., Scharenberg A.M. 2001. ADP-ribose gating of the calcium-permeable LTRPC2 channel revealed by Nudix motif homology. Nature 411:595–599CrossRefPubMedGoogle Scholar
  64. Perraud A.L., Knowles H.M., Schmitz C. 2004. Novel aspects of signaling and ion-homeostasis regulation in immunocytes. The TRPM ion channels and their potential role in modulating the immune response. Mol. Immunol. 41:657–673CrossRefPubMedGoogle Scholar
  65. Perraud A.L., Schmitz C., Scharenberg A.M. 2003. TRPM2 Ca2+ permeable cation channels: from gene to biological function. Cell Calcium 33:519–531CrossRefPubMedGoogle Scholar
  66. Perraud A.L., Takanishi C.L., Shen B., Kang S., Smith M.K., Schmitz C., Knowles H.M., Ferraris D., Li W., Zhang J., Stoddard B.L., Scharenberg A.M. 2005. Accumulation of free ADP-ribose from mitochondria mediates oxidative stress-induced gating of TRPM2 cation channels. J. Biol. Chem. 280:6138–6148CrossRefPubMedGoogle Scholar
  67. Petronilli V., Penzo D., Scorrano L., Bernardi P., Di Lisa F. 2001. The mitochondrial permeability transition, release of cytochrome c and cell death. Correlation with the duration of pore openings in situ. J. Biol. Chem. 276:12030–12034CrossRefPubMedGoogle Scholar
  68. Prawitt D., Enklaar T., Klemm G., Gartner B., Spangenberg C., Winterpacht A., Higgins M., Pelletier J., Zabel B. 2000. Identification and characterization of MTR1, a novel gene with homology to melastatin (MLSN1) and the trp gene family located in the BWS-WT2 critical region on chromosome 11p15.5 and showing allele-specific expression. Hum. Mol. Genet. 9:203–216CrossRefPubMedGoogle Scholar
  69. Rosker C., Graziani A., Lukas M., Eder P., Zhu M.X., Romanin C., Groschner K. 2004. Ca2+ signaling by TRPC3 involves Na+ entry and local coupling to the Na+/Ca2+ exchanger. J. Biol. Chem. 279:13696–13704CrossRefPubMedGoogle Scholar
  70. Runnels L.W., Yue L., Clapham D.E. 2001. TRP-PLIK, a bifunctional protein with kinase and ion channel activities. Science 291:1043–1047CrossRefPubMedGoogle Scholar
  71. Sano Y., Inamura K., Miyake A., Mochizuki S., Yokoi H., Matsushime H., Furuichi K. 2001. Immunocyte Ca2+ influx system mediated by LTRPC2. Science 293:1327–1330CrossRefPubMedGoogle Scholar
  72. Sattler M., Verma S., Shrikhande G., Byrne C.H., Pride Y.B., Winkler T., Greenfield E.A., Salgia R., Griffin J.D. 2000. The BCR/ABL tyrosine kinase induces production of reactive oxygen species in hematopoietic cells. J. Biol. Chem. 275:24273–24278CrossRefPubMedGoogle Scholar
  73. Schild L., Keilhoff G., Augustin W., Reiser G., Striggow F. 2001. Distinct Ca2+ thresholds determine cytochrome c release or permeability transition pore opening in brain mitochondria. FASEB J. 15:565–567PubMedGoogle Scholar
  74. Schlingmann K.P., Weber S., Peters M., Niemann Nejsum L., Vitzthum H., Klingel K., Kratz M., Haddad E., Ristoff E., Dinour D., Syrrou M., Nielsen S., Sassen M., Waldegger S., Seyberth H.W., Konrad M. 2002. Hypomagnesemia with secondary hypocalcemia is caused by mutations in TRPM6, a new member of the TRPM gene family. Nat. Genet. 31:166–170CrossRefPubMedGoogle Scholar
  75. Schmitz C., Perraud A.L. 2005. The TRPM cation channels in the immune context. Curr. Pharm. Des. 11:2765–2778CrossRefPubMedGoogle Scholar
  76. Schmitz C., Perraud A.L., Johnson C.O., Inabe K., Smith M.K., Penner R., Kurosaki T., Fleig A., Scharenberg A.M. 2003. Regulation of vertebrate cellular Mg2+ homeostasis by TRPM7. Cell 114:191–200CrossRefPubMedGoogle Scholar
  77. Scorrano L., Penzo D., Petronilli V., Pagano F., Bernardi P. 2001. Arachidonic acid causes cell death through the mitochondrial permeability transition. Implications for tumor necrosis factor-alpha aopototic signaling. J. Biol. Chem. 276:12035–12040CrossRefPubMedGoogle Scholar
  78. Stridh H., Kimland M., Jones D.P., Orrenius S., Hampton M.B. 1998. Cytochrome c release and caspase activation in hydrogen peroxide- and tributyltin-induced apoptosis. FEBS. Lett. 429:351–355CrossRefPubMedGoogle Scholar
  79. Strubing C., Krapivinsky G., Krapivinsky L., Clapham D.E. 2001. TRPC1 and TRPC5 form a novel cation channel in mammalian brain. Neuron 29:645–655CrossRefPubMedGoogle Scholar
  80. Tang J., Lin Y., Zhang Z., Tikunova S., Birnbaumer L., Zhu M.X. 2001. Identification of common binding sites for calmodulin and inositol 1,4,5–trisphosphate receptors on the carboxyl termini of trp channels. J. Biol. Chem. 276:21303–21310CrossRefPubMedGoogle Scholar
  81. Tang Y., Tang J., Chen Z., Trost C., Flockerzi V., Li M., Ramesh V., Zhu M.X. 2000. Association of mammalian trp4 and phospholipase C isozymes with a PDZ domain-containing protein, NHERF. J. Biol. Chem. 275:37559–37564CrossRefPubMedGoogle Scholar
  82. Tong Q., Chu X., Cheung J.Y., Conrad K., Stahl R., Barber D.L., Mignery G., Miller B.A. 2004. Erythropoietin-modulated calcium influx through TRPC2 is mediated by phospholipase Cgamma and IP3R. Am. J. Physiol. 287:C1667–1678CrossRefGoogle Scholar
  83. Tsavaler L., Shapero M.H., Morkowski S., Laus R. 2001. Trp-p8, a novel prostate-specific gene, is up-regulated in prostate cancer and other malignancies and shares high homology with transient receptor potential calcium channel proteins. Cancer. Res. 61:3760–3769PubMedGoogle Scholar
  84. Rossum D.B., Patterson R.L., Sharma S., Barrow R.K., Kornberg M., Gill D.L., Snyder S.H. 2005. Phospholipase Cgamma1 controls surface expression of TRPC3 through an intermolecular PH domain. Nature 434:99–104CrossRefPubMedGoogle Scholar
  85. Vazquez G., Wedel B.J., Kawasaki B.T., Bird G.S., Putney J.W., Jr. 2004. Obligatory role of Src kinase in the signaling mechanism for TRPC3 cation channels. J. Biol. Chem. 279:40521–40528CrossRefPubMedGoogle Scholar
  86. Vazquez G., Wedel B.J., Trebak M., St John Bird G., Putney J.W., Jr. 2003. Expression level of the canonical transient receptor potential 3 (TRPC3) channel determines its mechanism of activation. J. Biol. Chem. 278:21649–1654CrossRefPubMedGoogle Scholar
  87. Venkatachalam K., Ma H.T., Ford D.L., Gill D.L. 2001. Expression of functional receptor-coupled TRPC3 channels in DT40 triple receptor InsP3 knockout cells. J. Biol. Chem. 276:33980–3395CrossRefPubMedGoogle Scholar
  88. Voltz J.W., Weinman E.J., Shenolikar S. 2001. Expanding the role of NHERF, a PDZ-domain containing protein adapter, to growth regulation. Oncogene 20:6309–6314CrossRefPubMedGoogle Scholar
  89. Walder R.Y., Landau D., Meyer P., Shalev H., Tsolia M., Borochowitz Z., Boettger M.B., Beck G.E., Englehardt R.K., Carmi R., Sheffield V.C. 2002. Mutation of TRPM6 causes familial hypomagnesemia with secondary hypocalcemia. Nat. Genet. 31:171–174CrossRefPubMedGoogle Scholar
  90. Wehage E., Eisfeld J., Heiner I., Jungling E., Zitt C., Luckhoff A. 2002. Activation of the cation channel long transient receptor potential channel 2 (LTRPC2) by hydrogen peroxide. A splice variant reveals a mode of activation independent of ADP-ribose. J. Biol. Chem. 277:23150–23156CrossRefPubMedGoogle Scholar
  91. Yoon J., Ben-Ami H.C., Hong Y.S., Park S., Strong L.L., Bowman J., Geng C., Baek K., Minke B., Pak W.L. 2000. Novel mechanism of massive photoreceptor degeneration caused by mutations in the trp gene of Drosophila. J. Neurosci. 20:649–659Google Scholar
  92. Zhang W., Chu X., Tong Q., Cheung J.Y., Conrad K., Masker K., Miller B.A. 2003. A novel TRPM2 isoform inhibits calcium influx and susceptibility to cell death. J. Biol. Chem. 278:16222–16229CrossRefPubMedGoogle Scholar
  93. Zhang, W., Hirschler-Laszkiewicz, I., Tong, Q., Conrad, K., Sun, S.-C., Penn, L., Barber, D.L., Stahl, R., Carey, D.J., Cheung, J.Y., Miller, B.A. 2006. TRPM2 is an Ion Channel Which Modulates Hematopoietic Cell Death Through Activation of Caspases and PARP Cleavage. Am. J. Physiol. 290: C1146–C1159CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, Inc. 2006

Authors and Affiliations

  1. 1.The Departments of Pediatrics and Biochemistry and Molecular BiologyThe Pennsylvania State University College of MedicineHersheyUSA

Personalised recommendations