Abstract
Reactive oxygen species (ROS) are capable of affecting neuronal cell function and structure. Here, we investigated the direct effects of hydrogen peroxide (H2O2), one of the ROS, on axonal transport in cultured mouse dorsal root ganglion neurons using video-enhanced microscopy. Treatment of neurons with the H2O2 donor tert-butyl hydroperoxide (TBHP; 10 nM–1 mM) inhibited anterograde and retrograde movement of organelles in a time- and concentration-dependent manner. Mitochondria and lysosomes were clearly swollen by TBHP at 100 μM and 1 mM in association with complete and irreversible cessation of axonal transport. In contrast, cytoskeletal structures were apparently unchanged even at the highest TBHP concentration (1 mM). Lipid peroxides, detected by swallow-tailed perylene derivative fluorescence, were produced by TBHP in plasma membranes and more highly in organelle membranes. The TBHP-induced inhibition of axonal transport, lipid peroxide production, and organelle swelling were blocked by pretreatment with α-tocopherol (vitamin E, 1 mM). These results suggest that H2O2 inhibited axonal transport via lipid peroxidation along with degenerative changes in organelles.
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References
Avshalumov MV, Chen BT, Rice ME (2000) Mechanisms underlying H2O2-mediated inhibition of synaptic transmission in rat hippocampal slices. Brain Res 882:86–94
Banan A, Fields JZ, Farhadi A, Talmage DA, Zhang L, Keshavarzian A (2002) Activation of δ-isoform of protein kinase C is required for oxidant-induced disruption of both the microtubule cytoskeleton and permeability barrier of intestinal epithelia. J Pharmacol Exp Ther 303:17–28
Bergamini CM, Gambetti S, Dondi A, Cervellati C (2004) Oxygen, reactive oxygen species and tissue damage. Curr Pharm Des 10:1611–1626
Gahtan E, Auerbach JM, Groner Y, Segal M (1998) Reversible impairment of long-term potentiation in transgenic Cu/Zn-SOD mice. Eur J Neurosci 10:538–544
Galindo MF, Jordán J, González-García C, Ceña V (2003) Reactive oxygen species induce swelling and cytochrome c release but not transmembrane depolarization in isolated rat brain mitochondria. Br J Pharmacol 139:797–804
Gélinas S, Chapados C, Beauregard M, Gosselin I, Martinoli MG (2000) Effect of oxidative stress on stability and structure of neurofilament proteins. Biochem Cell Biol 78:667–674
Halliwell B, Cross CE (1994) Oxygen-derived species: their relation to human disease and environmental stress. Environ Health Perspect 102:5–12
Huot J, Houle F, Spitz DR, Landry J (1996) HSP27 phosphorylation-mediated resistance against actin fragmentation and cell death induced by oxidative stress. Cancer Res 56:273–279
Jezek P, Hlavatá L (2005) Mitochondria in homeostasis of reactive oxygen species in cell, tissues, and organism. Int J Biochem Cell Biol 37:2478–2503
Johansson A-C, Appelqvist H, Nilsson C, Kågedal K, Roberg K, Öllinger K (2010) Regulation of apoptosis-associated lysosomal membrane permeabilization. Apoptosis 15:527–540
Magrané G, Manfredi G (2009) Mitochondrial function, morphology, and axonal transport in amyotrophic lateral sclerosis. Antioxid Redox Signal 11:1615–1626
Mirabelli F, Salis A, Marinoni V, Finardi G, Bellomo G, Thor H, Orrenius S (1988) Menadione-induced bleb formation in hepatocytes is associated with the oxidation of thiol groups in actin. Arch Biochem Biophys 264:261–269
Ogawa Y, Kobayashi T, Kariya S, Nishioka A, Nakayama K, Seguchi H, Yoshida S (2004) Prevention of hydrogen peroxide-induced apoptosis of human peripheral T cells by a lysosomotropic iron chelator, ammonium chloride. Int J Mol Med 14:1007–1013
Pellmar TC, Hollinden GE, Sarvey JM (1991) Free radicals accelerate the decay of long-term potentiation in field CA1 of guinea-pig hippocampus. Neuroscience 44:353–359
Peng T-I, Jou M-J (2004) Mitochondrial swelling and generation of reactive oxygen species induced by photoirradiation are heterogeneously distributed. Ann NY Acad Sci 1011:112–122
Ratan RR, Murphy TH, Baraban JM (1994) Oxidative stress induces apoptosis in embryonic cortical neurons. J Neurochem 62:376–379
Roy S, Zhang B, Lee VM, Trojanowski JQ (2005) Axonal transport defects: a common theme in neurodegenerative diseases. Acta Neuropathol 109:5–13
Sayre LM, Perry G, Smith MA (2008) Oxidative stress and neurotoxicity. Chem Res Toxicol 21:172–188
Simonian NA, Coyle JT (1996) Oxidative stress in neurodegenerative diseases. Annu Rev Pharmacol Toxicol 36:83–106
Stokin GB, Goldstein LS (2006) Axonal transport and Alzheimer’s disease. Annu Rev Biochem 75:607–627
Takahashi T, Kitaoka K, Ogawa Y, Kobayashi T, Seguchi H, Tani T, Yoshida S (2004) Lysosomal dysfunction on hydrogen peroxide-induced apoptosis of osteoarthritic chondrocytes. Int J Mol Med 14:197–200
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Isonaka, R., Hiruma, H. & Kawakami, T. Inhibition of Axonal Transport Caused by tert-Butyl Hydroperoxide in Cultured Mouse Dorsal Root Ganglion Neurons. J Mol Neurosci 45, 194–201 (2011). https://doi.org/10.1007/s12031-010-9457-3
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DOI: https://doi.org/10.1007/s12031-010-9457-3