Sulfiredoxin-1 attenuates oxidative stress via Nrf2/ARE pathway and 2-Cys Prdxs after oxygen-glucose deprivation in astrocytes.

Abstract

Sulfiredoxin-1 (Srxn1), an endogenous antioxidant protein, is involved in keeping the balance of the cell's oxidation/reduction and can resist oxidative stress. However, the exact antioxidant effects of Srxn1 remain fully unclear. The study aims to examine the effects of Srxn1 on oxidative stress and explore the potential mechanisms in astrocytes with 6 h/oxygen-glucose deprivation (OGD), 24 h/respiration. In the study, silencing Srxn1 was performed before exposure to 6 h/OGD, 24 h/respiration in primary astrocytes. Decreased cell viability and increased cellular damage measured by CellTiter 96H AQueous Non-Radioactive Cell Proliferation Assay (MTS) and lactate dehydrogenase (LDH) were observed in Srxn1 silencing astrocytes. In addition, Srxn1 silencing resulted in a decrease in both intracellular superoxide dismutase (SOD) and glutathione (GSH). NF-E2-related factor 2 (Nrf2), a transcription factor known to influence susceptibility to oxidative stress, upregulated Srxn1 expression during oxidative stress caused by OGD in the astrocytes. Electromobility shift assay (EMSA) demonstrated a decreased binding of Nrf2 to oligomers containing Srxn1 ter-specific antioxidant response element (ARE)-binding site in Nrf2 silencing astrocytes. We also found that a reduction of peroxiredoxin (Prdx)-SO3 was closely dependent on Srxn1. In addition, 2-Cys Prdxs protein levels were increased in the astrocytes exposed to OGD, as evaluated by immunoblot analysis. All taken together, the study suggested that silencing Srxn1 would result into increasing sensitivity to OGD-induced oxidative stress injury in astrocytes. Furthermore, Nrf2/ARE pathway was involved into Srxn1, playing its antioxidant protection against oxidative stress, all of which would provide a novel therapeutic theory for treating acute ischemic brain injury.

• Authors: Yang Zhou, Song Duan, Yunchuan Zhou, Shanshan Yu, Jingxian Wu, Xiaoying Wu, Jing Zhao, Yong Zhao
• Journal: Journal of molecular neuroscience : MN (J Mol Neurosci) Vol. 55 Issue 4 Pg. 941-50 (Apr 2015) ISSN: 1559-1166 [Electronic] United States
• PMID: 25407820 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Glucose
• Glutathione
• Oxidoreductases Acting on Sulfur Group Donors
• Oxygen
• Peroxiredoxins
• Srxn1 protein, rat
• Superoxide Dismutase
• NF-E2-Related Factor 2

Topics

• Animals
• Rats
• Antioxidant Response Elements
• Astrocytes (metabolism)
• Cell Hypoxia
• Glucose (deficiency)
• Glutathione (metabolism)
• Oxidative Stress
• Oxidoreductases Acting on Sulfur Group Donors (genetics, metabolism)
• Oxygen (metabolism)
• Peroxiredoxins (genetics, metabolism)
• Rats, Wistar
• Superoxide Dismutase (genetics, metabolism)
• NF-E2-Related Factor 2 (genetics, metabolism)