NKX3.1 binding to GPX2, QSCN6, SOD1, and SOD2 promoters contributes to antioxidant response regulation via transactivation
TURKISH JOURNAL OF BIOLOGY
Authors: Butuner, Bilge Debelec; Korkmaz, Kemal Sami
Abstract
NKX3.1 is a prostate-specific transcription factor that is regulated by the androgen receptor in the presence of androgens. It functions as a tumor suppressor against the development of prostatic intraepithelial neoplasia and primary prostate tumors. Here, a recognized approach combining in silico analysis and chromatin immunoprecipitation (ChIP) was used to identify the genes directly regulated by NKX3.1 promoter binding in LNCaP cells. Quantitative PCR using ChIP-captured DNAs as templates verified a subset of NKX3.1 binding motifs. Thus, in the presence of androgens, significant NKX3.1 binding occurs to promoters of GPX2, QSCN6, SOD1, and SOD2 genes that contribute to oxidative stress regulation. Our data demonstrate that NKX3.1 is found in a DNA-bound state transiently at a basal level even in the absence of androgens; an increase in androgens promotes NKX3.1 binding, perhaps temporally rather than spatially, to the specific sites. The overall changes potentiate the transcriptional regulatory activity of NKX3.1, although they are dependent on the androgen receptor for the target promoters. The results suggest that NKX3.1 contributes to an antioxidant response by regulating the transcription of oxidative stress regulators by direct promoter binding.
The role of vitamin C in the gene expression of oxidative stress markers in fibroblasts from burn patients
ACTA CIRURGICA BRASILEIRA
Authors: Bonucci, Jessica; Gragnani, Alfredo; Trincado, Marcelo Moraes; Vincentin, Victor; Alves Correa, Silvana Aparecida; Ferreira, Lydia Masako
Abstract
Purpose: To assess the action of vitamin C on the expression of 84 oxidative stress related-genes in cultured skin fibroblasts from burn patients. Methods: Skin samples were obtained from ten burn patients. Human primary fibroblasts were isolated and cultured to be distributed into 2 groups: TF (n = 10, fibroblasts treated with vitamin C) and UF (n = 10, untreated fibroblasts). Gene expression analysis using quantitative polymerase chain reaction array was performed for comparisons between groups. Results: The comparison revealed 10 upregulated genes as follows: arachidonate 12-lipoxygenase (ALOX12), 24-dehydrocholesterol reductase (DHCR24), dual oxidase 1 (DUOX1), glutathione peroxidase 2 (GPX2), glutathione peroxidase 5 (GPX5), microsomal glutathione S-transferase 3 (MGST3), peroxiredoxin 4 (PRDX4), phosphatidylinositol-3,4,5-trisphosphate dependent Rac exchange factor 1 (P-REX1), prostaglandin-endoperoxide synthase 1 (PTGS1), and ring finger protein 7 (RNF7). Conclusion: Cultured fibroblasts obtained from burn patients and treated with vitamin C resulted in 10 differentially expressed genes, all overexpressed, with DUOX1, GPX5, GPX2 and PTGS1 being of most interest.