Anti-Human NFE2L2 polyclonal antibody

Astaxanthin (AST), a red dietary carotenoid, has synergistic antioxidant effects with polyunsaturated fatty acids at low concentrations via Nuclear factor (erythroid-derived 2)-like 2 (NFE2L2 or Nrf2)/antioxidant response element (ARE) signaling. In addition, chromatin remodeling and DNA methylation-based gene silencing represent a common mechanism in prostate carcinogenesis and tumor progression from normal cells to pre-initiated cells and ultimately to invasive carcinoma. Therefore, the control of epigenetic modification and the transcriptional/translational control of the activation of Nrf2 and Nrf2-target genes, including glutathione S-transferases (GSTs), appear to be an important mechanism that protects cells against injuries from oxidative stress and cancer development. In this study, we aim to investigate the role of AST in reactivating the expression of Nrf2 and GSTP1 through epigenetic modification in human prostate LNCaP cells. Treatment with AST in human LNCaP cells reduced the methylation of 21 CpG sites of the GSTP1 CpG island but did not affect the three CpG sites of the Nrf2 promoter region. AST induced the mRNA expression and protein expression of both Nrf2 and GSTP1. It also increased the mRNA expression of NQO1 in sh-mock LNCaP cells but not in sh-SETD7 LNCaP cells. Furthermore, AST reduced the protein expression of DNMT3b and significantly inhibited DNMT and HDAC activities in vitro. Taken together, these results suggest that AST decreased the methylation status of the GSTP1, and these epigenetic modifying effects may originate from the decreasing activities of epigenetic modification enzymes, contributing to the overall beneficial health effects of AST.

Macroautophagy/autophagy is an evolutionarily conserved cellular degradation and recycling process that is tightly regulated by external stimuli, diet, and stress. Our recent findings suggest that in C. elegans, a nutrient sensing pathway mediated by MTORC2 (mechanistic target of rapamycin kinase complex 2) and its downstream effector kinase SGK-1 (serum- and glucocorticoid-inducible kinase homolog 1) suppresses autophagy, involving mitophagy. Induced autophagy/mitophagy in MTORC2-deficient animals slows down development and impairs reproduction independently of the SGK-1 effectors DAF-16/FOXO and SKN-1/NFE2L2/NRF2. In this punctum, we discuss how TORC2-SGK-1 signaling might regulate autophagic turnover and its impact on mitochondrial homeostasis via linking mitochondria-derived reactive oxygen species (mtROS) production to mitophagic turnover.