This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Wang, J.
Right arrow Articles by Pantopoulos, K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Wang, J.
Right arrow Articles by Pantopoulos, K.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, March 2006, p. 1948-1954, Vol. 26, No. 5
0270-7306/06/$08.00+0     doi:10.1128/MCB.26.5.1948-1954.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Sodium Nitroprusside Promotes IRP2 Degradation via an Increase in Intracellular Iron and in the Absence of S Nitrosylation at C178

Jian Wang,1 Carine Fillebeen,1 Guohua Chen,1 Bill Andriopoulos,1 and Kostas Pantopoulos1,2*

Lady Davis Institute for Medical Research, Sir Mortimer B. Davis Jewish General Hospital, 3755 Cote-Ste-Catherine Road, Montreal, Quebec H3T 1E2, Canada,1 Department of Medicine, McGill University, Montreal, Quebec H3A 2T5, Canada2

Received 10 September 2005/ Returned for modification 9 October 2005/ Accepted 1 December 2005

In iron-replete cells the posttranscriptional regulator IRP2 undergoes ubiquitination and proteasomal degradation. A similar response occurs in cells exposed to sodium nitroprusside (SNP), an NO-releasing drug. It has been proposed that nitroprusside ([Fe(CN)5NO]2–) fails to donate iron into cells and that it promotes IRP2 degradation via S nitrosylation at C178. This residue is located within a stretch of 73 amino acids, earlier proposed to define an iron-dependent degradation domain. Surprisingly, we show that IRP2 bearing a C178S mutation or a {Delta}73 deletion is sensitive to degradation not only by ferric ammonium citrate (FAC) but also by SNP. Moreover, FAC and SNP attenuate the RNA-binding activities of IRP2 and its homologue IRP1 with similar kinetics. Actinomycin D, cycloheximide, succinylacetone, and dimethyl-oxalylglycine antagonize IRP2 degradation in response to both FAC and SNP, suggesting a common mechanistic basis. IRP2 is not only sensitive to fresh, but also to photodegraded SNP and remains unaffected by S-nitrosoglutathione (GSNO), an established nitrosation agent. Importantly, both fresh and photodegraded SNP, but not GSNO, promote a >4-fold increase in the calcein-accessible labile iron pool. Collectively, these results suggest that IRP2 degradation by SNP does not require S nitrosylation but rather represents a response to iron loading.

* Corresponding author. Mailing address: Lady Davis Institute for Medical Research, Sir Mortimer B. Davis Jewish General Hospital, 3755 Cote-Ste-Catherine Rd., Montreal, Quebec H3T 1E2, Canada. Phone: (514) 340-8260, ext. 5293. Fax: (514) 340-7502. E-mail: kostas.pantopoulos{at}mcgill.ca.

Molecular and Cellular Biology, March 2006, p. 1948-1954, Vol. 26, No. 5
0022-538X/06/$08.00+0     doi:10.1128/MCB.26.5.1948-1954.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Cardaci, S., Filomeni, G., Rotilio, G., Ciriolo, M. R. (2008). Reactive Oxygen Species Mediate p53 Activation and Apoptosis Induced by Sodium Nitroprusside in SH-SY5Y Cells. Mol. Pharmacol. 74: 1234-1245 [Abstract] [Full Text]  
  • Jasid, S., Simontacchi, M., Puntarulo, S. (2008). Exposure to nitric oxide protects against oxidative damage but increases the labile iron pool in sorghum embryonic axes. J Exp Bot 0: ern235v1-ern235 [Abstract] [Full Text]  
  • Niles, B. J., Clegg, M. S., Hanna, L. A., Chou, S. S., Momma, T. Y., Hong, H., Keen, C. L. (2008). Zinc Deficiency-induced Iron Accumulation, a Consequence of Alterations in Iron Regulatory Protein-binding Activity, Iron Transporters, and Iron Storage Proteins. J. Biol. Chem. 283: 5168-5177 [Abstract] [Full Text]  
  • Wang, J., Fillebeen, C., Chen, G., Biederbick, A., Lill, R., Pantopoulos, K. (2007). Iron-Dependent Degradation of Apo-IRP1 by the Ubiquitin-Proteasome Pathway. Mol. Cell. Biol. 27: 2423-2430 [Abstract] [Full Text]  
  • (2006). Correction to "No Nitric Oxide for HO-1 from Sodium Nitroprusside". Mol. Pharmacol. 70: 434-434 [Full Text]  
  • Kim, H. J., Tsoy, I., Park, M. K., Lee, Y. S., Lee, J. H., Seo, H. G., Chang, K. C. (2006). Iron Released by Sodium Nitroprusside Contributes to Heme Oxygenase-1 Induction via the cAMP-Protein Kinase A-Mitogen-Activated Protein Kinase Pathway in RAW 264.7 Cells. Mol. Pharmacol. 69: 1633-1640 [Abstract] [Full Text]  
  • Schroder, H. (2006). No Nitric Oxide for HO-1 from Sodium Nitroprusside. Mol. Pharmacol. 69: 1507-1509 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»