The DOI matches its Crossref record; 9 of the 9 references it cites were found in a registry or an index.
S-Nitrosylation-dependent Inactivation of Akt/Protein Kinase B in Insulin Resistance
Open accessAbstract
Inducible nitric-oxide synthase (iNOS) has been implicated in many human diseases including insulin resistance. However, how iNOS causes or exacerbates insulin resistance remains largely unknown. Protein S-nitrosylation is now recognized as a prototype of a redox-dependent, cGMP-independent signaling component that mediates a variety of actions of nitric oxide (NO). Here we describe the mechanism of inactivation of Akt/protein kinase B (PKB) in NO donor-treated cells and diabetic (db/db) mice. NO donors induced S-nitrosylation and inactivation of Akt/PKB in vitro and in intact cells. The inhibitory effects of NO donor were independent of phosphatidylinositol 3-kinase and cGMP. In contrast, the concomitant presence of oxidative stress accelerated S-nitrosylation and inactivation of Akt/PKB. In vitro denitrosylation with reducing agent reactivated recombinant and cellular Akt/PKB from NO donor-treated cells. Mutated Akt1/PKBalpha (C224S), in which cysteine 224 was substituted by serine, was resistant to NO donor-induced S-nitrosylation and inactivation, indicating that cysteine 224 is a major S-nitrosylation acceptor site. In addition, S-nitrosylation of Akt/PKB was increased in skeletal muscle of diabetic (db/db) mice compared with wild-type mice. These data suggest that S-nitrosylation-mediated inactivation may contribute to the pathogenesis of iNOS- and/or oxidative stress-involved insulin resistance.
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Cited by
Reactive oxygen species have a causal role in multiple forms of insulin resistance
Houstis, N., Rosen, E. D., & Lander, E. S. (2006) · Nature · doi:10.1038/nature04634 · Cited by 2,525
Redox regulation of cell survival
Trachootham, D., Lu, W., Ogasawara, M. A., Valle, N. R.-D., & Huang, P. (2008) · Antioxidants & Redox Signaling · doi:10.1089/ars.2007.1957 · Cited by 1,781
Inflammation and insulin resistance
de Luca, C., & Olefsky, J. M. (2008) · FEBS Letters · doi:10.1016/j.febslet.2007.11.057 · Cited by 1,161
Protein S-nitrosylation in health and disease: a current perspective
Foster, M. W., Hess, D. T., & Stamler, J. S. (2009) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2009.06.007 · Cited by 752
Lee, Y. S., Kim, J.-W., Osborne, O., Oh, D. Y., Sasik, R., Schenk, S., Chen, A., Chung, H., Murphy, A., Watkins, S. M., et al. (2014) · Cell · doi:10.1016/j.cell.2014.05.012 · Cited by 598
Metadata
- Authors
- Yasukawa, T., Tokunaga, E., Ota, H., Sugita, H., Martyn, J. A. J., & Kaneki, M.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2005-03
- Volume
- 280
- Issue
- 9
- Pages
- 7511-7518
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2094054841
- Cited by
- 261
- References
- 9
- FWCI
- 5.07
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Yasukawa, T., Tokunaga, E., Ota, H., Sugita, H., Martyn, J. A. J., & Kaneki, M. (2005). S-Nitrosylation-dependent Inactivation of Akt/Protein Kinase B in Insulin Resistance. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m411871200
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