Recently, somatic mutations that activate NFE2L2, including mutations in <i>NFE2L2, KEAP1</i>, or <i>CUL3</i>, have been found to be associated with poor outcomes in patients with non-small cell lung cancer (NSCLC).
Erastin and APAP promoted NSCLC cell death by regulating nucleus translocation of nuclear factor erythroid 2-related factor 2 (Nrf2); and the ferroptosis induced by erastin and APAP was abrogated by bardoxolone methyl (BM) with less generation of reactive oxygen species and malondialdehyde.
To clarify metabolic features of NRF2-activated lung cancers, we conducted targeted metabolomic (T-Met) and global metabolomic (G-Met) analyses of non-small-cell lung cancer (NSCLC) cell lines in combination with exome and transcriptome analyses.
Several Nrf2 activators are at various stages of clinical development and are being tested in clinical trials for chronic kidney disease (CKD) including diabetic kidney disease, Alport syndrome, autosomal dominant polycystic kidney disease and focal segmental glomerulosclerosis.
In non-small cell lung cancer (NSCLC) cells and xenografts, MKP-1 knockdown triggered the down-regulation of the metabolic enzymes and cytoprotective proteins, which are the target genes of Nrf2.
SIGNIFICANCE: This study identifies pathways activated by Nrf2 that are important for the proliferation and tumorigenicity of KEAP1-mutant non-small cell lung cancer.
Taken together, our results indicate that the Nestin-Keap1-Nrf2 axis regulates cellular redox homeostasis and confers oxidative stress resistance in NSCLC.
Finally, we report that NRF2 protein expression in a NSCLC cohort exceeds the typical incidence of combined NRF2, KEAP1, and CUL3 mutations, and that NRF2 expression in this cohort is correlated with PIDD levels.
This study demonstrates that the NRF2 pathway may serve as a therapeutic target in NSCLC, and ginseng compounds may be effective for the treatment of this disease.
Using multiple isogenic non-small cell lung cancer (NSCLC) cell lines, we observed a reduction of Nrf2 protein and activity in a prometastatic mesenchymal cell state and increased reactive oxygen species.
Sitagliptin may induce HO-1 expression via activation of PI3K and Nrf2 in rats with diabetic nephropathy; HO-1 can improve the oxidative stress of diabetic nephropathy, eventually protect from diabetic nephropathy.
Moreover, our findings provided a fuller understanding of the regulatory role of NF-κB and Nrf2 in DN, indicating that they could be important therapeutic targets.
Deletion of the Nrf2 gene completely abrogated the efficacies of SRT2104 and PFT-α in elevating antioxidants and ameliorating DN, despite their abilities to activate SIRT1 and inhibit P53 in the Nrf2 KO mice.
Multiple metabolic pathways of DKD have been evaluated with varying success; including mitochondrial function, reactive oxygen species, NADPH oxidase (NOX), transcription factors (NF-B and Nrf2), advanced glycation, protein kinase C (PKC), aldose reductase, JAK-STAT, autophagy, apoptosis-signaling kinase 1 (ASK1), fibrosis and epigenetics.
Bergenin can inhibit glucose-induced ECM production in glomerular mesangial cells through the down-regulation of oxidative stress via the mTOR/β-TrcP/Nrf2 pathway, and it might be a candidate drug for the prevention and treatment of DN.
The aim of this study was to evaluate the renoprotective effects of hesperetin against DN in rats, and to investigate mechanisms from the aspect of Nrf2/ARE/Glo-1 pathway.