Similar Patterns of Mitochondrial Vulnerability and Rescue Induced by Genetic Modification of α-Synuclein, Parkin, and DJ-1 inCaenorhabditis elegans
作者： Rina Ved , Shamol Saha , Beth Westlund , Celine Perier , Lucinda Burnam
关键词:
摘要: How genetic and environmental factors interact in Parkinson disease is poorly understood. We have now compared the patterns of vulnerability rescue Caenorhabditis elegans with modifications three different implicated (PD). observed that expressing alpha-synuclein, deleting parkin (K08E3.7), or knocking down DJ-1 (B0432.2) produces similar pharmacological rescue. C. lines these changes were more vulnerable than nontransgenic nematodes to mitochondrial complex I inhibitors, including rotenone, fenperoximate, pyridaben, stigmatellin. In contrast, manipulations did not increase sensitivity paraquat, sodium azide, divalent metal ions (Fe(II) Cu(II)), etoposide nematodes. Each PD-related was also partially rescued by antioxidant probucol, II activator, D-beta-hydroxybutyrate, anti-apoptotic bile acid tauroursodeoxycholic acid. Complete protection all achieved combining d-beta-hydroxybutyrate but probucol. These results show diverse disrupt function elegans, they raise possibility disruption a pathway shared common many types familial PD.
highwire.org参考文章(67)
AB Singleton, M Farrer, J Johnson, A Singleton, S Hague, J Kachergus, M Hulihan, T Peuralinna, A Dutra, R Nussbaum, S Lincoln, A Crawley, M Hanson, D Maraganore, C Adler, MR Cookson, M Muenter, M Baptista, D Miller, J Blancato, J Hardy, K Gwinn-Hardy, None, α-Synuclein Locus Triplication Causes Parkinson's Disease Science. ,vol. 302, pp. 841- 841 ,(2003) , 10.1126/SCIENCE.1090278
Arnaud M. Labrousse, Mauro D. Zappaterra, Daniel A. Rube, Alexander M. van der Bliek, C. elegans dynamin-related protein DRP-1 controls severing of the mitochondrial outer membrane. Molecular Cell. ,vol. 4, pp. 815- 826 ,(1999) , 10.1016/S1097-2765(00)80391-3
Andrew G. Fraser, Ravi S. Kamath, Peder Zipperlen, Maruxa Martinez-Campos, Marc Sohrmann, Julie Ahringer, Functional genomic analysis of C. elegans chromosome I by systematic RNA interference Nature. ,vol. 408, pp. 325- 330 ,(2000) , 10.1038/35042517
Ali Naini, Serge Przedborski, Kim Tieu, Casper Caspersen, Miquel Vila, Celine Perier, Vernice Jackson-Lewis, Ravichandran Ramasamy, Peter Teismann, Shi-Du Yan, Du-Chu Wu, D-β-Hydroxybutyrate rescues mitochondrial respiration and mitigates features of Parkinson disease Journal of Clinical Investigation. ,vol. 112, pp. 892- 901 ,(2003) , 10.1172/JCI18797
Enza Maria Valente, Patrick M Abou-Sleiman, Viviana Caputo, Miratul MK Muqit, Kirsten Harvey, Suzana Gispert, Zeeshan Ali, Domenico Del Turco, Anna Rita Bentivoglio, Daniel G Healy, Alberto Albanese, Robert Nussbaum, Rafael González-Maldonado, Thomas Deller, Sergio Salvi, Pietro Cortelli, William P Gilks, David S Latchman, Robert J Harvey, Bruno Dallapiccola, Georg Auburger, Nicholas W Wood, Hereditary Early-Onset Parkinson's Disease Caused by Mutations in PINK1 Science. ,vol. 304, pp. 1158- 1160 ,(2004) , 10.1126/SCIENCE.1096284
James J. Palacino, Dijana Sagi, Matthew S. Goldberg, Stefan Krauss, Claudia Motz, Maik Wacker, Joachim Klose, Jie Shen, Mitochondrial Dysfunction and Oxidative Damage in parkin-deficient Mice Journal of Biological Chemistry. ,vol. 279, pp. 18614- 18622 ,(2004) , 10.1074/JBC.M401135200
Mihael H Polymeropoulos, Christian Lavedan, Elisabeth Leroy, Susan E Ide, Anindya Dehejia, Amalia Dutra, Brian Pike, Holly Root, Jeffrey Rubenstein, Rebecca Boyer, Edward S Stenroos, Settara Chandrasekharappa, Aglaia Athanassiadou, Theodore Papapetropoulos, William G Johnson, Alice M Lazzarini, Roger C Duvoisin, Giuseppe Di Iorio, Lawrence I Golbe, Robert L Nussbaum, Mutation in the α-synuclein gene identified in families with Parkinson's disease Science. ,vol. 276, pp. 2045- 2047 ,(1997) , 10.1126/SCIENCE.276.5321.2045
Cecília M. P. Rodrigues, Susana Solá, Juanita C. Sharpe, José J. G. Moura, Clifford J. Steer, Tauroursodeoxycholic acid prevents Bax-induced membrane perturbation and cytochrome C release in isolated mitochondria. Biochemistry. ,vol. 42, pp. 3070- 3080 ,(2003) , 10.1021/BI026979D
Daekyun Lee, Sun-Young Lee, Eui-Nam Lee, Chung-Soon Chang, Seung R. Paik, α‐Synuclein exhibits competitive interaction between calmodulin and synthetic membranes Journal of Neurochemistry. ,vol. 82, pp. 1007- 1017 ,(2004) , 10.1046/J.1471-4159.2002.01024.X
R L Barnhart, S J Busch, R L Jackson, Concentration-dependent antioxidant activity of probucol in low density lipoproteins in vitro: probucol degradation precedes lipoprotein oxidation. Journal of Lipid Research. ,vol. 30, pp. 1703- 1710 ,(1989) , 10.1016/S0022-2275(20)38219-5