Publications by authors named "Eriko Naganuma"
Heme oxygenase 1 (HO-1) is the key enzyme for heme catabolism and cytoprotection. Whereas gene expression in response to various stresses has been investigated extensively, the precise mechanisms by which gene expression is regulated by the HO-1 substrate heme remain elusive. To systematically examine whether stress-mediated induction and substrate-mediated induction of utilize similar or distinct regulatory pathways, we developed an HO-1-DsRed-knock-in reporter mouse in which the gene is floxed by loxP sites and the gene has been inserted.
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View Article and Find Full Text PDFSpace flight produces an extreme environment with unique stressors, but little is known about how our body responds to these stresses. While there are many intractable limitations for in-flight space research, some can be overcome by utilizing gene knockout-disease model mice. Here, we report how deletion of Nrf2, a master regulator of stress defense pathways, affects the health of mice transported for a stay in the International Space Station (ISS).
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- Nrf2 is important for regulating how cells deal with oxidative stress, and its overactivation due to the loss of Keap1 can lead to severe health issues in mice.
- Removing Nrf2 from the oesophagus in Keap1-null mice allows them to survive but leads to kidney problems, such as polyuria and hydronephrosis, due to lower levels of aquaporin 2, which is crucial for water reabsorption.
- The study indicates that controlling Nrf2 activity during development is essential for kidney health and suggests that specific ablation of Nrf2 could help create animal models to explore new functions of this protein.
Article Synopsis
- The Keap1-Nrf2 system is crucial for protecting cells from oxidative and electrophilic stresses, utilizing specific cysteine residues in Keap1 as sensors.
- Researchers identified mutations in two cysteine residues (Cys273 and Cys288) that allow Keap1 to still repress Nrf2 while also analyzing their functionality.
- The study categorized chemical inducers of Nrf2 into four classes based on which cysteine residues they require, highlighting that Keap1 employs these residues both individually and together to react to various environmental stresses.
Sickle cell disease (SCD) is an inherited disorder caused by a point mutation in the β-globin gene, leading to the production of abnormally shaped red blood cells. Sickle cells are prone to hemolysis and thereby release free heme into plasma, causing oxidative stress and inflammation that in turn result in damage to multiple organs. The transcription factor Nrf2 (nuclear factor erythroid 2-related factor 2) is a master regulator of the antioxidant cell-defense system.
View Article and Find Full Text PDFBackground: NFE2-related factor 2 (Nrf2) is a master regulatory transcription factor for antioxidant genes. Inhibition of its adaptor protein, Kelch-like ECH-associated protein 1 (Keap1), activates Nrf2. Podocyte injury triggers the progressive deterioration of glomerular damage toward glomerulosclerosis.
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