Abbreviated Journal Title
Proc. Natl. Acad. Sci. U. S. A.
Keywords
apoptosis; peroxynitrite; PC12 cells; AMYOTROPHIC-LATERAL-SCLEROSIS; SPINAL-CORD-INJURY; PEROXYNITRITE-INDUCED; APOPTOSIS; PROTEIN-TYROSINE NITRATION; MOTOR-NEURON APOPTOSIS; NITRIC-OXIDE; PC12 CELLS; SUPEROXIDE-DISMUTASE; INCREASED; 3-NITROTYROSINE; CHAPERONE MACHINERY; Multidisciplinary Sciences
Abstract
Oxidative stress is a widely recognized cause of cell death associated with neurodegeneration, inflammation, and aging. Tyrosine nitration in these conditions has been reported extensively, but whether tyrosine nitration is a marker or plays a role in the cell-death processes was unknown. Here, we show that nitration of a single tyrosine residue on a small proportion of 90-kDa heat-shock protein (Hsp90), is sufficient to induce motor neuron death by the P2X7 receptor-dependent activation of the Fas pathway. Nitrotyrosine at position 33 or 56 stimulates a toxic gain of function that turns Hsp90 into a toxic protein. Using an antibody that recognizes the nitrated Hsp90, we found immunoreactivity in motor neurons of patients with amyotrophic lateral sclerosis, in an animal model of amyotrophic lateral sclerosis, and after experimental spinal cord injury. Our findings reveal that cell death can be triggered by nitration of a single protein and highlight nitrated Hsp90 as a potential target for the development of effective therapies for a large number of pathologies.
Journal Title
Proceedings of the National Academy of Sciences of the United States of America
Volume
110
Issue/Number
12
Publication Date
1-1-2013
Document Type
Article
Language
English
First Page
E1102
Last Page
E1111
WOS Identifier
ISSN
0027-8424
Recommended Citation
Franco, Maria Clara; Ye, Yaozu; Refakis, Christian A.; Feldman, Jessica L.; Stokes, Audrey L.; Fernandez de Mera, Raquel M. Melero; Sparrow, Nicklaus A.; Callingasan, Noel Y.; Kiaei, Mahmoud; Rhoads, Timonthy W.; Ma, Thong C.; Grumet, Martin; Barnes, Stephen; Beal, M. Flint; Beckman, Joseph S.; Mehl, Ryan; and Estevez, Alvaro G., "Nitration of Hsp90 induces cell death" (2013). Faculty Bibliography 2010s. 3989.
https://stars.library.ucf.edu/facultybib2010/3989
Comments
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