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S-Glutathionylation of estrogen receptor α affects dendritic cell function.
- Source :
-
Journal of Biological Chemistry . 3/23/2018, Vol. 293 Issue 12, p4366-4380. 15p. - Publication Year :
- 2018
-
Abstract
- Glutathione S-transferase Pi (GSTP) is a thiolase that catalyzes the addition of glutathione (GSH) to receptive cysteines in target proteins, producing an S-glutathionylated residue. Accordingly, previous studies have reported that S-glutathionylation is constitutively decreased in cells from mice lacking GSTP (Gstp1/p2+/+). Here, we found that bone marrow-derived dendritic cells (BMDDCs) from Gstp1/p2-/- mice have proliferation rates that are greater than those in theirWTcounterparts (Gstp1/p2-/-). Moreover, Gstp1/p2-/- BMDDCs had increased reactive oxygen species (ROS) levels and decreased GSH:glutathione disulfide (GSSG) ratios. Estrogen receptor α (ERα) is linked to myeloproliferation and differentiation, and we observed that its steady-state levels are elevated in Gstp1/p2-/- BMDDCs, indicating a link betweenGSTPand ERα activities. BMDDCs differentiated by granulocyte-macrophage colony-stimulating factor had elevated ERα levels, which were more pronounced in Gstp1/p2-/- thanWTmice. When stimulated with lipopolysaccharide for maturation, Gstp1/p2-/- BMDDCs exhibited augmented endocytosis, maturation rate, cytokine secretion, and T-cell activation; heightened glucose uptake and glycolysis; increased Akt signaling (in the mTOR pathway); and decreased AMPK-mediated phosphorylation of proteins. Of note, GSTP formed a complex with ERα, stimulating ERα S-glutathionylation at cysteines 221, 245, 417, and 447; altering ERα's binding affinity for estradiol; and reducing overall binding potential (receptor density and affinity) 3-fold. Moreover, in Gstp1/p2-/- BMDDCs, ERα S-glutathionylation was constitutively decreased. Taken together, these findings suggest that GSTP-mediated S-glutathionylation of ERα controls BMDDC differentiation and affects metabolic function in dendritic cells. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00219258
- Volume :
- 293
- Issue :
- 12
- Database :
- Academic Search Index
- Journal :
- Journal of Biological Chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 128748072
- Full Text :
- https://doi.org/10.1074/jbc.M117.814327