These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: The glutathionylation of p65 modulates NF-κB activity in 15-deoxy-Δ¹²,¹⁴-prostaglandin J₂-treated endothelial cells.
    Author: Lin YC, Huang GD, Hsieh CW, Wung BS.
    Journal: Free Radic Biol Med; 2012 May 01; 52(9):1844-53. PubMed ID: 22387200.
    Abstract:
    Protein glutathionylation is a posttranslational modification of cysteine residues with glutathione in response to mild oxidative stress. Because 15-deoxy-Δ12,14-prostaglandin J(2) (15d-PGJ(2)) is an electrophilic prostaglandin that can increase glutathione (GSH) levels and augment reactive oxygen species (ROS) production, we hypothesized that it induces NF-κB-p65 glutathionylation and would exert anti-inflammatory effects. Herein, we show that 15d-PGJ(2) suppresses the expression of ICAM-1 and NF-κB-p65 nuclear translocation. 15d-PGJ(2) upregulates the Nrf2-related glutathione synthase gene and thereby increases the GSH levels. Consistent with this, Nrf2 siRNA molecules abolish the inhibition of p65 nuclear translocation in 15d-PGJ(2)-induced endothelial cells (ECs). ECs treated with GSSG show increased thiol modifications of p65 and also a block in TNFα-induced p65 nuclear translocation and ICAM-1 expression, but not in IκBα degradation. However, the overexpression of glutaredoxin 1 was found to be accompanied by a modest increase in NF-κB activity. Furthermore, we found that multiple cysteine residues in p65 are responsible for glutathionylation. 15d-PGJ(2) was observed to induce p65 glutathionylation and is suppressed by a GSH synthesis inhibitor, buthionine sulfoximine, by catalase, and by Nrf2 siRNA molecules. Our results thus indicate that the GSH/ROS-dependent glutathionylation of p65 is likely to be responsible for 15d-PGJ(2)-mediated NF-κB inactivation and for the enhanced inhibitory effects of 15d-PGJ(2) on TNFα-treated ECs.
    [Abstract] [Full Text] [Related] [New Search]