Human Molecular Genetics, Vol 8, 425-430, Copyright © 1999 by Oxford University Press
A Wong, J Yang, P Cavadini, C Gellera, B Lonnerdal, F Taroni and G Cortopassi
Expansions of an intronic GAA repeat reduce the expression of frataxin and
cause Friedreich's ataxia (FRDA), an autosomal recessive neurodegenerative
disease. Frataxin is a mitochondrial protein, and disruption of a frataxin
homolog in yeast results in increased sensitivity to oxidant stress,
increased mitochondrial iron and respiration deficiency. These previous
data support the hypothesis that FRDA is a disease of mitochondrial
oxidative stress, a hypothesis we have tested in cultured cells from FRDA
patients. FRDA fibroblasts were hypersensitive to iron stress and
significantly more sensitive to hydrogen peroxide than controls. The iron
chelator deferoxamine rescued FRDA fibroblasts more than controls from
oxidant-induced death, consistent with a role for iron in the differential
kinetics of death; however, mean mitochondrial iron content in FRDA
fibroblasts was increased by only 40%. Treatment of cells with the
intracellular Ca2+chelator BAPTA-AM rescued both FRDA fibroblasts and
controls from oxidant-induced death. Treatment with apoptosis inhibitors
rescued FRDA but not control fibroblasts from oxidant stress, and
staurosporine- induced caspase 3 activity was higher in FRDA fibroblasts,
consistent with the possibility that an apoptotic step upstream of caspase
3 is activated in FRDA fibroblasts. These results demonstrate that FRDA
fibroblasts are sensitive to oxidant stress, and may be a useful model in
which to elucidate the FRDA mechanism and therapeutic strategies.
ARTICLES
The Friedreich's ataxia mutation confers cellular sensitivity to oxidant stress which is rescued by chelators of iron and calcium and inhibitors of apoptosis
Department of Molecular Biosciences, 1311 Haring Hall, University of California, Davis, CA 95616, USA.
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|
|
|
|
|
|
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|
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|
|
 |
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|
|
|
|
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|
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|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
 |
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
G. Tan, E. Napoli, F. Taroni, and G. Cortopassi Decreased expression of genes involved in sulfur amino acid metabolism in frataxin-deficient cells Hum. Mol. Genet., July 15, 2003; 12(14): 1699 - 1711. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
E. Cabiscol, G. Belli, J. Tamarit, P. Echave, E. Herrero, and J. Ros Mitochondrial Hsp60, Resistance to Oxidative Stress, and the Labile Iron Pool Are Closely Connected in Saccharomyces cerevisiae J. Biol. Chem., November 8, 2002; 277(46): 44531 - 44538. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Pianese, L. Busino, I. De Biase, T. de Cristofaro, M. S. Lo Casale, P. Giuliano, A. Monticelli, M. Turano, C. Criscuolo, A. Filla, et al. Up-regulation of c-Jun N-terminal kinase pathway in Friedreich's ataxia cells Hum. Mol. Genet., November 1, 2002; 11(23): 2989 - 2996. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
|
|
E. M. Becker, J. M. Greer, P. Ponka, and D. R. Richardson Erythroid differentiation and protoporphyrin IX down-regulate frataxin expression in Friend cells: characterization of frataxin expression compared to molecules involved in iron metabolism and hemoglobinization Blood, May 15, 2002; 99(10): 3813 - 3822. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G Tozzi, M Nuccetelli, M Lo Bello, S Bernardini, L Bellincampi, S Ballerini, L M Gaeta, C Casali, A Pastore, G Federici, et al. Antioxidant enzymes in blood of patients with Friedreich's ataxia Arch. Dis. Child., May 1, 2002; 86(5): 376 - 379. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. A. Shoichet, A. T. Baumer, D. Stamenkovic, H. Sauer, A. F. H. Pfeiffer, C. R. Kahn, D. Muller-Wieland, C. Richter, and M. Ristow Frataxin promotes antioxidant defense in a thiol-dependent manner resulting in diminished malignant transformation in vitro Hum. Mol. Genet., April 1, 2002; 11(7): 815 - 821. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Cavadini, H. A. O'Neill, O. Benada, and G. Isaya Assembly and iron-binding properties of human frataxin, the protein deficient in Friedreich ataxia Hum. Mol. Genet., February 1, 2002; 11(3): 217 - 227. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Chantrel-Groussard, V. Geromel, H. Puccio, M. Koenig, A. Munnich, A. Rotig, and P. Rustin Disabled early recruitment of antioxidant defenses in Friedreich's ataxia Hum. Mol. Genet., September 1, 2001; 10(19): 2061 - 2067. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Tan, L.-S. Chen, B. Lonnerdal, C. Gellera, F. A. Taroni, and G. A. Cortopassi Frataxin expression rescues mitochondrial dysfunctions in FRDA cells Hum. Mol. Genet., September 1, 2001; 10(19): 2099 - 2107. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Sherer and J. T. Greenamyre A therapeutic target and biomarker in Friedreich's ataxia Neurology, December 12, 2000; 55(11): 1600 - 1601. [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. Sobrido and D. H. Geschwind Molecular Genetics and Inherited Ataxias: Redefining Phenotypes and Pathogenesis Neuroscientist, December 1, 2000; 6(6): 465 - 474. [Abstract] [PDF]
|
|
|
|
|
|
M. A POOK, S. A H AL-MAHDAWI, N. H THOMAS, R. APPLETON, A. NORMAN, R. MOUNTFORD, and S. CHAMBERLAIN Identification of three novel frameshift mutations in patients with Friedreich's ataxia J. Med. Genet., November 1, 2000; 37(11): 38e - 38. [Full Text]
|
|
|
|
|
|
P. Cavadini, C. Gellera, P. I. Patel, and G. Isaya Human frataxin maintains mitochondrial iron homeostasis in Saccharomyces cerevisiae Hum. Mol. Genet., October 1, 2000; 9(17): 2523 - 2530. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. T. Jensen and V. C. Culotta Role of Saccharomyces cerevisiae ISA1 and ISA2 in Iron Homeostasis Mol. Cell. Biol., June 1, 2000; 20(11): 3918 - 3927. [Abstract] [Full Text]
|
|
|
|
|
|
C. J. Cummings and H. Y. Zoghbi Fourteen and counting: unraveling trinucleotide repeat diseases Hum. Mol. Genet., April 1, 2000; 9(6): 909 - 916. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. S. Chen and J. Kaplan CCC1 Suppresses Mitochondrial Damage in the Yeast Model of Friedreich's Ataxia by Limiting Mitochondrial Iron Accumulation J. Biol. Chem., March 10, 2000; 275(11): 7626 - 7632. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. B Delatycki, R. Williamson, and S. M Forrest Friedreich ataxia: an overview J. Med. Genet., January 1, 2000; 37(1): 1 - 8. [Abstract] [Full Text]
|
|
|
|
|
|
J. Kaplan Friedreich's ataxia is a mitochondrial disorder PNAS, September 28, 1999; 96(20): 10948 - 10949. [Full Text] [PDF]
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|
|
|
|
S. S. Branda, P. Cavadini, J. Adamec, F. Kalousek, F. Taroni, and G. Isaya Yeast and Human Frataxin Are Processed to Mature Form in Two Sequential Steps by the Mitochondrial Processing Peptidase J. Biol. Chem., August 6, 1999; 274(32): 22763 - 22769. [Abstract] [Full Text] [PDF]
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|
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S. Dhe-Paganon, R. Shigeta, Y.-I. Chi, M. Ristow, and S. E. Shoelson Crystal Structure of Human Frataxin J. Biol. Chem., September 29, 2000; 275(40): 30753 - 30756. [Abstract] [Full Text] [PDF]
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