Nörolojik Hücrelerde TRPM2 Katyon Kanallarının Moleküler Mekanizmalardaki Rolleri

Nörolojik Hücrelerde TRPM2 Katyon Kanallarının Moleküler Mekanizmalardaki Rolleri

Vücuttaki tüm organlar özellikle merkezi sinir sistemi, serbest radikal hasarına karşı duyarlıdır. Beynin yüksek oksijen tüketimi, kolayca okside olabilen zengin yağ asitlerini barındırması, diğer organlara göre düşük seviyede antioksidan enzim ve antioksidan içermesi onu serbest oksijen radikalleri tarafından birincil hedef haline getirmektedir. Na+ ve Ca+2 iyonlarına geçirgen melastatine bağlı “transient receptor potential 2 (TRPM2)” katyon kanalları ya Ca+2 ile uyum içinde olan ADP-riboz tarafından ya da oksidatif stres (H2O2) tarafından kanalların enzimatik Nudix bölgesine bağladığı ve ADP-riboz pirofosfataz’ın aktive olduğu rapor edilmiştir. Bu enzim aktivasyonu sonucunda da TRPM2 kanallarının açıldığı gözlemlenmiştir. Bu derleme çalışmasında, nöronal hücrelerde, TRPM2 inhibisyonuna yol açtığı düşünülen ADPR ve H2O2 maddeleri tam anlaşılmadığı için nörolojik hastalıklardaki bipolar hastalıklar kadar mikroglia, hipokampus ve beyindeki ADPR ve oksidatif stresin TRPM2 kanalları üzerindeki etkileri gözden geçirilmiştir. Mikroglia ve hipokampal hücrelerde TRPM2 katyon kanallarının hem ADPR hem de H2O2 tarafından açıldığı gözlemlendi. Buna ek olarak, nörolojik hastalıklarda H2O2 nin TRPM2 aktivasyonundan sorumlu olduğu gözüküyor. Bipolar hastalıkların etiyolojisinde genetik faktörler önemli rollere sahip olabilirler.

___

  • Bond, C.E., Greenfield. S.A., 2007. Multiple cascade effects of oxidative stress on astroglia. Glia. 55, 1348-1361.
  • Butterfield, D.A., 2003. Amyloid beta-peptide [1-42]-associated free radical-induced oxidative stres and neurodegeneration in Alzheimer’s disease brain: mechanisms and consequences. Curr. Med. Chem. 10, 2651-2659.
  • Chanock, S.J., Roesler, J., Zhan, S., Hopkins, P., Lee, P., Barrett, D.T., Christensen, B.L., Curnutte, J.T., Görlach, A., 2000. Genomic structure of the human p47-phox (NCF1) gene. Blood Cells Mol. Dis. 26, 37-46.
  • Clapham, D.E., 2003. TRP channels as cellular sensors. Nature. 426, 517-524.
  • Clapham, D.E., 2007. Snapshot: mammalian TRP channels. Cell. 129, 220.
  • 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, 715-723.
  • Gasser, A., Glassmeier, G., Fliegert, R., Langhorst, M.F., Meinke, S., Hein, D., Kruger, S., Weber, K., Heiner, I., Oppenheimer, N., Schwarz, J.R., Guse, A.H., 2006. Activation of T cell calcium influx by the second messenger ADP-ribose. J. Biol. Hem. 281, 2489-2496.
  • Guse, A.H., 2005. Second messenger function and the structure-activity relationship of cyclic adenosine diphosphoribose (cADPR). FEBS J. 272, 4590-4597.
  • Halliwell, B., 2006. Oxidative stress and neurodegeneration: where are we now? J. Neurochem. 97, 1634-1658.
  • 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, 163-73.
  • Heiner, I., Eisfeld, J., Luckhoff ,A., 2003. Role and regulation of TRP channels in neutrophil granulocytes. Cell. Calcium. 33, 533- 40.
  • Heiner, I., Eisfeld, J., Warnstedt, M., Radukina, N., Jungling, E., Luckhoff, A., 2006. Endogenous ADP-ribose enables calcium- regulated cation currents through TRPM2 channels in neutrophil granulocytes. Biochem. J. 398, 225-232.
  • Hill, K., Tigue, N.J., Kelsell, R.E., Benham, C.D., McNulty, S., Schaefer, M., Randall, A.D., 2006. Characterization of recombinant rat TRPM2 and a TRPM2-like conductance in cultured rat striatal neurons. Neuropharmacol. 50, 89-97.
  • Inamura, K., Sano, Y., Mochizuki, S., Yokoi, H., Miyake, A., Nozawa, K., Kitada, C., Matsushime, H., Furuichi, K., 2003. Response to ADP-ribose by activation of TRPM2 in the CRI-G1 insulinoma cell line. J. Membr. Biol. 191, 201-207.
  • Kaneko, S., Kawakami, S., Hara, Y., Wakamori, M., Itoh, E., Minami, T,, Takada, Y., Kume, T., Katsuki, H., Mori, Y., Akaike, A., 2006. A critical role of TRPM2 in neuronal cell death by hydrogen peroxide. J. Pharmacol. Sci. 101, 66-76.
  • 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.
  • Kraft, R., Grimm, C., Grosse, K., Hoffmann, A., Sauerbruch, S., Kettenmann, H., Schultz, G., Harteneck, C., 2004. Hydrogen pe- roxide and ADP-ribose induce TRPM2-mediated calcium influx and cation currents in microglia. Am. J. Physiol. Cell. Physiol. 286, 129-137.
  • Kraft, R., Harteneck, C., 2005. The mammalian melastatin-related transient receptor potential cation channels: an overview. Pflugers Arch. 451, 204-211.
  • Kühn, F.J., Heiner, I., Luckhoff, A., 2005. TRPM2: a calcium influx pathway regulated by oxidative stress and the novel second messenger ADP-ribose. Pflugers Arch. 451, 212-219.
  • Kühn, F.J., Lückhoff, A., 2004. Sites of the NUDT9-H domain critical for ADP-ribose activation of the cation channel TRPM2. J. Biol. Chem. 279, 46431-46437.
  • Massullo, P., Sumoza-Toledo, A., Bhagat, H., Partida-Sánchez, S., 2006. TRPM channels, calcium and redox sensors during innate immune responses. Semin Cell. Dev. Biol. 17, 654-666.
  • Morale, M.C., Serra, P.A., L’episcopo, F., Tirolo, C., Caniglia, S., Testa, N., Gennuso, F., Giaquinta, G., Rocchitta, G., Desole, M.S., Miele, E., Marchetti, B., 2006. Estrogen, neuroinflammation and neuroprotection in Parkinson’s disease: glia dictates resistance versus vulnerability to neurodegeneration. Neurosci. 138, 869-878.
  • Naziroglu, M., Lückhoff, A., Jungling, E., 2007. Antagonist effect of flufenamic acid on TRPM2 cation channels activated by hydro- gen peroxide. Cell. Biochem Funct. 25, 383-387.
  • Nazıroğlu, M., Lückhoff, A., 2008a. A calcium influx pathway regulated separately by oxidative stress and ADP- ribose in TRPM2 channels: Single channel events. Neurochem Res. 33, 1256-1262.
  • Nazıroğlu, M., Lückhoff, A., 2008b. Effects of antioxidants on calcium influx through TRPM2 channels in transfected cells activa- ted by hydrogen peroxide. J. Neurological. Sci. 270, 152-158.
  • Nazıroğlu, M., 2007a. Molecular Mechanisms of vitamin E on intracellular signaling pathways in brain. In Reactive Oxygen Species and Diseases. Ed.; Laszlo Goth, Res. Signpost Press: Kerala, India. pp 239-256.
  • Naziroglu, M., 2007b. New molecular mechanisms on the activation of TRPM2 channels by oxidative stress and ADP-ribose. Ne- urochem Res. 32, 1990-2001.
  • Nazıroğlu, M., 2009. Role of selenium on calcium signaling and oxidative stress- induced molecular pathways in epilepsy. Neuroc- hem Res. 34, 2181–2191.
  • Nazıroğlu, M., 2010. Effects of vitamin C on oxidative stress-induced molecular pathways in epilepsy. Editor: Christina M. Jackson. In: Vitamin C: Nutrition, Side Effects and Supplements. Nova Science Publishers, Inc. ISBN: 978-1-61728-754-1.
  • Nilius, B., Owsianik, G., Voets, T., Peters, J.A., 2007. Transient Receptor Potential cation channels in disease. Physiol. Rev. 87, 165–217.
  • Nilius, B., 2007. TRP channels in disease. Biochem Biophys. Acta. 1772, 805-812.
  • Ohana, L., Newell, E.W., Stanley, E.F., Schlichter, L.C., 2009. The Ca2+ release-activated Ca2+ current (ICRAC) mediates store- operated Ca2+ entry in rat microglia. Channels. 3, 129-139.
  • Olah, M.E., Jackson, M.F., Li, H., Perez, Y., Sun, H.S., Kiyonaka, S., Mori, Y., Tymianski, M., MacDonald, J.F., 2009. Ca2+- dependent induction of TRPM2 currents in hippocampal neurons. J. Physiol. 587, 965-979.
  • Özmen, I., Nazıroğlu, M., Alicı, H.A., Sahin, F., Cengiz, M., Eren, İ., 2007. Spinal morphine administration reduces the fatty acid contents in spinal cord and brain in rabbits due to oxidative stress. Neurochem Res. 32, 19-25.
  • Peier, A.M., Moqrich, A., Hergarden, A.C., Reeve, A.J., Andersson, D.A., Story, G.M., Earley, T.J., Dragoni, I., McIntyre, P., Bevan, S., Patapoutian, A., 2002. A TRP channel that senses cold stimuli and menthol.Cell. 108, 705-715.
  • 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 homo- logy. Nature. 411, 595-599.
  • Perraud, A.L., Schmitz, C., Scharenberg, A.M., 2003. TRPM2 Ca2+ permeable cation channels: from gene to biological function. Cell Calcium. 33, 519-531.
  • Perraud, A.L., Takanishi, C.L., Shen, B., Kang, S., Smith, M.K., Schmitz, C., Knowles, H.M., Ferraris, D., Li, W., Zhang, J., Stod- dard, 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, 6138-6148.
  • Rayman, M.P., 2009. Selenoproteins and human health: Insights from epidemiological data. Biochim Biophys Acta. 1790, 1533- 1540.
  • Smith, M.A., Herson, P.S., Lee, K., Pinnock, R.D., Ashford, M.L., 2003. Hydrogen-peroxide-induced toxicity of rat striatal neurons involves activation of a nonselective cation channel. J. Physiol. 547, 417-425.
  • Spencer, P.S., Nunn, P.B., Hugon, J., Ludolph, A.C., Ross, S.M., Roy, D.N., Robertson, R.C., 1987. Guam amyotrophic lateral sclerosis-parkinsonism-dementia linked to a plant excitant neurotoxin. Sci. 237, 517–522.
  • Staaf, S., Franck, M.C., Marmigère, F., Mattsson, J.P., Ernfors, P., 2010. Dynamic expression of the TRPM subgroup of ion channels in developing mouse sensory neurons. Gene Expr Patterns 10, 65-74.
  • Tafti, M., Ghyselinck, N.B., 2007. Functional implication of the vitamin A signaling pathway in the brain. Arch. Neurol. 64, 1706- 7611.
  • Togashi, K., Hara, Y., Tominaga, T., Higashi, T., Konishi, Y., Mori, Y., Tominaga, M., 2006. TRPM2 activation by cyclic ADP-ribose at body temperature is involved in insulin secretion. EMBO J. 25, 1804-1815.
  • Watanabe, H., Murakami, M., Ohba, T., Takahashi, Y., Ito, H., 2008. TRP Channel and cardiovascular disease. Pharmacol. Therap 118, 337-351.
  • Wehage, E., Eisfeld, J., Heiner, I., Jüngling, E., Zitt, C., Lückhoff, 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, 23150-23156.
  • Yamamoto, S., Shimizu, S., Kiyonaka, S., Takahashi, N., Wajima, T., Hara, Y., Negoro, T., Hiroi, T., Kiuchi, Y., Okada, T., Kaneko, S., Lange, I., Fleig, A., Penner, R., Nishi, M., Takeshima, H., Mori, Y., 2008. TRPM2-mediated Ca2+influx induces chemokine production in monocytes that aggravates inflammatory neutrophil infiltration. 14, 738-747.