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2013 | 73 | 4 |

Tytuł artykułu

Dynein c1h1, dynactin and syntaphilin expression in brain areas related to neurodegenerative diseases following exposure to rotenone

Warianty tytułu

Języki publikacji



Neurodegeneration is often accompanied by protein inclusions which may interfere with cell physiology. On the other hand, alteration in intracellular trafficking may precede impairment of neurotransmission and therefore trigger cell death. In view of this, it is hypothesized that changes in mitochondrial traffic may occur before neurodegeneration triggered by rotenone exposure and could favor this process. The effects of low concentrations of rotenone on the expression of dynein clhl, dynactin and syntaphilin, which are proteins related to mitochondria transport and anchoring, were evaluated in cell cultures of substantia nigra, locus coeruleus and hippocampus as well as in these same brain areas in Lewis aged rats. The results indicate that low concentrations of rotenone decrease dynein clhl protein levels in cell cultures and brain areas of aged rats. Dynactin is decreased after exposure to 0.1 and 0.3 nM of rotenone, and increased after exposure to 0.5 nM of rotenone in cell cultures. Aged rats present increased dynactin expression. Syntaphilin expression decreased in vitro and increased in vivo after rotenone exposure. These findings suggest that changes in protein expression related to mitochondrial retrograde transport and anchoring occur before neurodegeneration induced by rotenone exposure, which may be a primary factor to trigger neurodegenerative mechanisms.








Opis fizyczny



  • Department of Genetics and Evolutionary Biology, Institute for Biosciences, University of Sao Paulo, Sao Paulo, SP, Brazil
  • Department of Genetics and Evolutionary Biology, Institute for Biosciences, University of Sao Paulo, Sao Paulo, SP, Brazil
  • Department of Genetics and Evolutionary Biology, Institute for Biosciences, University of Sao Paulo, Sao Paulo, SP, Brazil
  • Department of Genetics and Evolutionary Biology, Institute for Biosciences, University of Sao Paulo, Sao Paulo, SP, Brazil
  • Department of Genetics and Evolutionary Biology, Institute for Biosciences, University of Sao Paulo, Sao Paulo, SP, Brazil


  • Abou-Sleiman PM, Muqit MM, Wood NW (2006) Expanding insights of mitochondrial dysfunction in Parkinson's dis¬ease. Nat Rev Neurosci 7: 207-219.
  • Amiri M, Hollenbeck PJ (2008) Mitochondrial biogenesis in the axons of vertebrate peripheral neurons. Dev Neurobiol 68: 1348-1361.
  • Arduino DM, Esteves AR, Cardoso SM (2011) Mitochondrial fusion/fission, transport and autophagy in Parkinson's disease: when mitochondria get nasty. Parkinsons Dis 2011: 767230.
  • Arnold B, Cassady SJ, VanLaar VS, Berman SB (2011) Integrating multiple aspects of mitochondrial dynamics in neurons: age-related differences and dynamic changes in a chronic rotenone model. Neurobiol Dis 41: 189-200.
  • Bilsland LG, Sahai E, Kelly G, Golding M, Greensmith L, Schiavo G (2010) Deficits in axonal transport precede ALS symptoms in vivo. Proc Natl Acad Sci U S A 107: 20523-20528.
  • Borland MK, Trimmer PA, Rubinstein JD, Keeney PM, Mohanakumar K, Liu L, Bennett JP, Jr. (2008) Chronic, low-dose rotenone reproduces Lewy neurites found in early stages of Parkinson's disease, reduces mitochon¬
  • drial movement and slowly kills differentiated SH-SY5Y neural cells. Mol Neurodegener 3: 21.
  • Bowling AC, Beal MF (1995) Bioenergetic and oxidative stress in neurodegenerative diseases. Life Sci 56: 1151¬1171.
  • Braunstein KE, Eschbach J, Rona-Voros K, Soylu R, Mikrouli E, Larmet Y, Rene F, De Aguilar JL, Loeffler JP, Muller HP, Bucher S, Kaulisch T, Niessen HG, Tillmanns J, Fischer K, Schwalenstocker B, Kassubek J, Pichler B, Stiller D, Petersen A, Ludolph AC, Dupuis L (2010) A point mutation in the dynein heavy chain gene leads to striatal atrophy and compromises neurite outgrowth of striatal neurons. Hum Mol Genet 19: 4385-4398.
  • Cannon JR, Tapias V, Na HM, Honick AS, Drolet RE, Greenamyre JT (2009) A highly reproducible rotenone model of Parkinson's disease. Neurobiol Dis 34: 279-290.
  • Cartelli D, Ronchi C, Maggioni MG, Rodighiero S, Giavini E, Cappelletti G (2010) Microtubule dysfunction pre¬cedes transport impairment and mitochondria damage in MPP+ -induced neurodegeneration. J Neurochem 115: 247-258.
  • Chaves RS, Melo TQ, Martins SA, Ferrari MF (2010) Protein aggregation containing beta-amyloid, alpha-synu- clein and hyperphosphorylated tau in cultured cells of hippocampus, substantia nigra and locus coeruleus after rotenone exposure. BMC Neurosci 11: 144.
  • Cho D-H, Nakamura T, Lipton S (2010) Mitochondrial dynamics in cell death and neurodegeneration. Cell Mol Life Sci 67: 3435-3447.
  • Choi WS, Palmiter RD, Xia Z (2011) Loss of mitochondrial complex I activity potentiates dopamine neuron death induced by microtubule dysfunction in a Parkinson's dis¬ease model. J Cell Biol 192: 873-882.
  • Chou AP, Li S, Fitzmaurice AG, Bronstein JM (2010) Mechanisms of rotenone-induced proteasome inhibition. Neurotoxicology 31: 367-372.
  • Demers G, Griffin G, De Vroey G, Haywood JR, Zurlo J, Bedard M (2006) Animal research. Harmonization of animal care and use guidance. Science 312: 700-701.
  • Deng W, Garrett C, Dombert B, Soura V, Banks G, Fisher EM, van der Brug MP, Hafezparast M (2010) Neurodegenerative mutation in cytoplasmic dynein alters its organization and dynein-dynactin and dynein-kinesin interactions. J Biol Chem 285: 39922-39934.
  • Diaz-Corrales FJ, Asanuma M, Miyazaki I, Miyoshi K, Ogawa N (2005) Rotenone induces aggregation of [gamma]- tubulin protein and subsequent disorganization of the centrosome: Relevance to formation of inclusion bodies and neurodegeneration. Neuroscience 133: 117-135.
  • Drolet RE, Cannon JR, Montero L, Greenamyre JT (2009) Chronic rotenone exposure reproduces Parkinson's dis¬ease gastrointestinal neuropathology. Neurobiol Dis 36: 96-102.
  • Eschbach J, Dupuis L (2011) Cytoplasmic dynein in neuro¬degeneration. Pharmacol Ther 130: 348-363.
  • Hollenbeck PJ, Saxton WM (2005) The axonal transport of mitochondria. J Cell Sci 118: 5411-5419.
  • Hollerhage M, Matusch A, Champy P, Lombes A, Ruberg M, Oertel WH, Hoglinger GU (2009) Natural lipophilic inhibitors of mitochondrial complex I are candidate tox¬ins for sporadic neurodegenerative tau pathologies. Exp Neurol 220: 133-142.
  • Kang JS, Tian JH, Pan PY, Zald P, Li C, Deng C, Sheng ZH (2008) Docking of axonal mitochondria by syntaphilin controls their mobility and affects short-term facilitation. Cell 132: 137-148.
  • Kimura N, Inoue M, Okabayashi S, Ono F, Negishi T (2009) Dynein dysfunction induces endocytic pathology accom¬panied by an increase in Rab GTPases: a potential mech¬anism underlying age-dependent endocytic dysfunction. J Biol Chem 284: 31291-31302.
  • Kivell BM, McDonald FJ, Miller JH (2001) Method for serum-free culture of late fetal and early postnatal rat brainstem neurons. Brain Res Brain Res Protoc 6: 91-99.
  • Lao G, Scheuss V, Gerwin CM, Su Q, Mochida S, Rettig J, Sheng ZH (2000) Syntaphilin: a syntaxin-1 clamp that controls SNARE assembly. Neuron 25: 191-201.
  • Leeuwenburgh C, Pamplona R, Sanz A (2011) Mitochondria and aging. J Aging Res 2011: 782946.
  • Lodi R, Schapira AH, Manners D, Styles P, Wood NW, Taylor DJ, Warner TT (2000) Abnormal in vivo skeletal muscle energy metabolism in Huntington's disease and dentatorubropallidoluysian atrophy. Ann Neurol 48: 72-76.
  • Mancuso M, Orsucci D, Siciliano G, Murri L (2008) Mitochondria, mitochondrial DNA and Alzheimer's dis¬ease. What comes first? Curr Alzheimer Res 5: 457-468.
  • Martin LJ (2007) Transgenic mice with human mutant genes causing Parkinson's disease and amyotrophic lateral scle¬rosis provide common insight into mechanisms of motor neuron selective vulnerability to degeneration. Rev Neurosci 18: 115-136.
  • Massaad CA, Amin SK, Hu L, Mei Y, Klann E, Pautler RG (2010) Mitochondrial superoxide contributes to blood flow and axonal transport deficits in the Tg2576 mouse model of Alzheimer's disease. PLoS One 5: e10561.
  • Melo T, Dunhao A, Martins S, Farizatto KG, Chaves R, Ferrari MR (2012) Rotenone-dependent changes of anterograde motor protein expression and mitochondrial mobility in brain areas related to neurodegenerative dis¬eases. Cell Mol Neurobiol 33: 327-335
  • Morfini G, Pigino G, Opalach K, Serulle Y, Moreira JE, Sugimori M, Llinas RR, Brady ST (2007) 1-Methyl-4- phenylpyridinium affects fast axonal transport by activa¬tion of caspase and protein kinase C. Proc Natl Acad Sci U S A 104: 2442-2447.
  • Radad K, Gille G, Rausch WD (2008) Dopaminergic neu¬rons are preferentially sensitive to long-term rotenone toxicity in primary cell culture. Toxicol In Vitro 22: 68-74.
  • Ravikumar B, Acevedo-Arozena A, Imarisio S, Berger Z, Vacher C, O'Kane CJ, Brown SD, Rubinsztein DC (2005) Dynein mutations impair autophagic clear¬ance of aggregate-prone proteins. Nat Genet 37: 771-776.
  • Ren Y, Feng J (2007) Rotenone selectively kills serotonergic neurons through a microtubule-dependent mechanism. J Neurochem 103: 303-311.
  • Ren Y, Liu W, Jiang H, Jiang Q, Feng J (2005) Selective vulnerability of dopaminergic neurons to microtubule depolymerization. J Biol Chem 280: 34105-34112.
  • Rizzardini M, Lupi M, Mangolini A, Babetto E, Ubezio P, Cantoni L (2006) Neurodegeneration induced by
  • complex I inhibition in a cellular model of familial amyotrophic lateral sclerosis. Brain Res Bull 69: 465-474.
  • Ross CA, Poirier MA (2005) Opinion: What is the role of protein aggregation in neurodegeneration? Nat Rev Mol Cell Biol 6: 891-898.
  • Schon EA, Przedborski S (2011) Mitochondria: the next (neurode)generation. Neuron 70: 1033-1053.
  • Smith TS, Bennett JP, Jr. (1997) Mitochondrial toxins in models of neurodegenerative diseases. I: In vivo brain hydroxyl radical production during systemic MPTP treat¬ment or following microdialysis infusion of methylpyri- dinium or azide ions. Brain Res 765: 183-188.
  • Srivastava P, Panda D (2007) Rotenone inhibits mam¬malian cell proliferation by inhibiting microtubule assembly through tubulin binding. FEBS Journal 274: 4788-4801.
  • Ullrich C, Humpel C (2009) Rotenone induces cell death of cholinergic neurons in an organotypic co-culture brain slice model. Neurochem Res 34: 2147-2153.
  • Van Laar VS, Berman SB (2009) Mitochondrial dynamics in Parkinson's disease. Exp Neurol 218: 247-256.
  • Weber TA, Reichert AS (2010) Impaired quality control of mitochondria: aging from a new perspective. Exp Gerontol 45: 503-511.
  • Williamson TL, Cleveland DW (1999) Slowing of axonal transport is a very early event in the toxicity of ALS-linked SOD1 mutants to motor neurons. Nat Neurosci 2: 50-56.
  • Xie W, Li X, Li C, Zhu W, Jankovic J, Le W (2010) Proteasome inhibition modeling nigral neuron degenera¬tion in Parkinson's disease. J Neurochem 115: 188-199.
  • Zhu YB, Sheng ZH (2011) Increased axonal mitochondrial mobility does not slow ALS-like disease in mutant SOD1 mice. J Biol Chem 286: 23432-23440.

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