Nuclear glutaredoxin 3 is critical for protection against oxidative stress-induced cell death.

Abstract

Mammalian glutaredoxin 3 (Grx3) has been shown to be critical in maintaining redox homeostasis and regulating cell survival pathways in cancer cells. However, the regulation of Grx3 is not fully understood. In the present study, we investigate the subcellular localization of Grx3 under normal growth and oxidative stress conditions. Both fluorescence imaging of Grx3-RFP fusion and Western blot analysis of cellular fractionation indicate that Grx3 is predominantly localized in the cytoplasm under normal growth conditions, whereas under oxidizing conditions, Grx3 is translocated into and accumulated in the nucleus. Grx3 nuclear accumulation was reversible in a redox-dependent fashion. Further analysis indicates that neither the N-terminal Trx-like domain nor the two catalytic cysteine residues in the active CGFS motif of Grx3 are involved in its nuclear translocation. Decreased levels of Grx3 render cells susceptible to cellular oxidative stress, whereas overexpression of nuclear-targeted Grx3 is sufficient to suppress cells' sensitivity to oxidant treatments and reduce reactive oxygen species production. These findings provide novel insights into the regulation of Grx3, which is crucial for cell survival against environmental insults.

• Authors: Khanh Pham, Rituraj Pal, Ying Qu, Xi Liu, Han Yu, Stephen L Shiao, Xinquan Wang, E O'Brian Smith, Xiaojiang Cui, George G Rodney, Ninghui Cheng
• Journal: Free radical biology & medicine (Free Radic Biol Med) Vol. 85 Pg. 197-206 (Aug 2015) ISSN: 1873-4596 [Electronic] United States
• PMID: 25975981 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical References

• Carrier Proteins
• GLRX3 protein, human
• Reactive Oxygen Species

Topics

• Carrier Proteins (metabolism)
• Cell Line, Tumor
• Cell Nucleus (metabolism)
• Humans
• Oxidative Stress
• Reactive Oxygen Species (metabolism)
• Subcellular Fractions (metabolism)