Nitric oxide induces thioredoxin-1 nuclear translocation: Possible association with the p21Ras survival pathway
- Departamento de Bioquimica/Biologia Molecular-CINTERGEN Universidade Federal de S.Paulo/Escola Paulista de Medicina, Sao Paulo (Brazil)
- Department of Biological Responses, Institute for Virus Research, Kyoto University, Kyoto (Japan)
- Instituto do Coracao, Incor, Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo (Brazil)
- Department of Pharmacology, New York University School of Medicine, New York (United States)
One of the major redox-regulating molecules with thiol reducing activity is thioredoxin-1 (TRX-1). TRX-1 is a multifunctional protein that exists in the extracellular millieu, cytoplasm, and nucleus, and has a distinct role in each environment. It is well known that TRX-1 promptly migrates to the nuclear compartment in cells exposed to oxidants. However, the intracellular location of TRX-1 in cells exposed to nitrosothiols has not been investigated. Here, we demonstrated that the exposure of HeLa cells to increasing concentrations of the nitrosothiol S-nitroso-N-acetylpenicillamine (SNAP) promoted TRX-1 nuclear accumulation. The SNAP-induced TRX-1 translocation to the nucleus was inhibited by FPTIII, a selective inhibitor of p21Ras. Furthermore, TRX-1 migration was attenuated in cells stably transfected with NO insensitive p21Ras (p21{sup RasC118S}). Downstream to p21Ras, the MAP Kinases ERK1/2 were activated by SNAP under conditions that promote TRX-1 nuclear translocation. Inhibition of MEK prevented SNAP-stimulated ERK1/2 activation and TRX-1 nuclear migration. In addition, cells treated with p21Ras or MEK inhibitor showed increased susceptibility to cell death induced by SNAP. In conclusion, our observations suggest that the nuclear translocation of TRX-1 is induced by SNAP involving p21Ras survival pathway.
- OSTI ID:
- 20854498
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 348, Issue 4; Other Information: DOI: 10.1016/j.bbrc.2006.07.178; PII: S0006-291X(06)01703-7; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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