In conclusion, TRPM2 channels were constitutively activated by intracellular ADPR currents in mice native megakaryocyte.
📌 3 Maddede Bu Makale
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Amaç & Hipotez:Since the mechanisms that lead to melastatin-like transient receptor potential 2 (TRPM2) channel activation in response to ADP-Ribose (ADPR) are not understood, I tested the effects of ADP-Ribose on TRPM2 cation channel currents in native bone marrow megakaryocyte of mice.
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Temel Bulgular & Veri:Kv1.3-deficient mice megakaryocyte cells were freshly isolated from bone marrow and the cells studied with the conventional whole-cell patch clamp technique.
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Sonuç & Katkı:In conclusion, TRPM2 channels were constitutively activated by intracellular ADPR currents in mice native megakaryocyte.
🔬Tür:Araştırma Makalesi
📍Kapsam:Genişletilmiş Akademik Örneklem
⚙️Değişkenler:TRPM2 channels · ADP-Ribose · bone marrow
Abstract
Since the mechanisms that lead to melastatin-like transient receptor potential 2 (TRPM2) channel activation in response to ADP-Ribose (ADPR) are not understood, I tested the effects of ADP-Ribose on TRPM2 cation channel currents in native bone marrow megakaryocyte of mice. Kv1.3-deficient mice megakaryocyte cells were freshly isolated from bone marrow and the cells studied with the conventional whole-cell patch clamp technique. ADPR (1mM) was applied intracellularly through the pipette. Non-selective cation currents in the mice were consistently induced by ADPR. Current density of ADPR in the cells were significantly (p<0.001) higher than in control. The time courses of ADPR effects in the mice were characterized by a delay of 3.66 ± 0.69. In conclusion, TRPM2 channels were constitutively activated by intracellular ADPR currents in mice native megakaryocyte.
Bai JZ, Lipski J. 2010. Differential expression of TRPM2 and TRPV4 channels and their potential role in oxidative stress-induced cell death in organotypic hippocampal culture. Neurotoxicology 31:204-214.
Buelow B, Song Y, Scharenberg AM. 2008. The Poly(ADP-ribose) polymerase PARP-1 is required for oxidative stress-induced TRPM2 activation in lymphocytes. J Biol Chem. 283:24571-24583.
Carter RN, Tolhurst G, Walmsley G, Vizuete-Forster M, Miller N, Mahaut-Smith MP. 2006. Molecular and electrophysiological characterization of transient receptor potential ion channels in the primary murine megakaryocyte. J Physiol. 576:151-162. Guse AH. 2005. Second messenger function and the structure-activity relationship of cyclic adenosine diphosphoribose (cADPR). FEBS J 272: 4590-4597.
Hara Y, Wakamori M, Ishii M, Maeno E, Nishida M, Yoshida T, et al., 2002. LTRPC2 Ca2+-permeable channel activated by changes in redox status confers susceptibility to cell death. Mol Cell 9: 163-173.
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. Ishii M, Shimizu S, Hara Y, Hagiwara T, Miyazaki A, Mori Y, Kiuchi Y. 2006. Intracellular-produced hydroxyl radical mediates H2O2-induced Ca2+ influx and cell death in rat beta-cell line RIN-5F. Cell Calcium 39:487-494. Mahaut-Smith MP. 2004. Patch-clamp recordings of electrophysiological events in the platelet and megakaryocyte. Methods Mol Biol. 273:277-300. Nazıroğlu M. 2007. New molecular mechanisms on the activation of TRPM2 channels by oxidative stress and ADP-ribose. Neurochem Res 32:1990- 2001.
Nazıroğlu M, Lückhoff A. 2008a. Effects of antioxidants on calcium influx through TRPM2 channels in transfected cells activated by hydrogen peroxide. J Neurol Sci 270:152-158.
Nazıroğlu M, Lückhoff A. 2008b. 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. 2010. TRPM2 cation channels, oxidative stress and neurological diseases: where are we now? Neurochem Res DOI: 10.1007/s11064-010- 0347-4.
Perraud AL, Fleig A, Dunn CA, Bagley LA, Launay P, Schmitz C, Stokes AJ, Zhu Q, Bessman MJ, Penner R, Kinet JP, Scharenberg AM. 2001. ADP-ribose gating of the calcium-permeable LTRPC2 channel revealed by Nudix motif homology. Nature 411:595-599.