Akira Uruno

Transcription factor Nrf2 (NF-E2-related factor 2) regulates a broad cytoprotective response to environmental stresses. Keap1 (Kelch-like ECH-associated protein 1) is an adaptor protein for cullin3-based ubiquitin E3 ligase and negatively regulates Nrf2. Whereas the Keap1-Nrf2 system plays important roles in oxidative stress response and metabolism, the roles Nrf2 plays in the prevention of diabetes mellitus remain elusive. Here we show that genetic activation of Nrf2 signaling by Keap1 gene hyp

Transcription factor Nrf2 (NF-E2-related factor 2) regulates wide-ranging cytoprotective genes in response to environmental stress. Keap1 (Kelch-like ECH-associated protein 1) is an adaptor protein for Cullin3-based ubiquitin E3 ligase and negatively regulates Nrf2. The Keap1-Nrf2 system plays important roles in the oxidative stress response and metabolism. However, the roles Nrf2 plays in prevention of pancreatic β-cell damage remain elusive. To demonstrate the roles of Nrf2 in pancreatic β-cel

Nrf2 (NF-E2-related-factor 2) is a stress-responsive transcription factor that protects cells against oxidative stresses. To clarify whether Nrf2 prevents Alzheimer's disease (AD), AD model <i>App^{NL-G-F/NL-G-F}</i> knock-in (<i>App^NLGF</i> ) mice were studied in combination with genetic Nrf2 induction model <i>Keap1^FA/FA</i> mice. While <i>App^NLGF</i> mice displayed shorter latency to escape than wild-type mice in the passive-avoidance task, the impairm

Nrf2 (NF-E2-related factor 2) contributes to the maintenance of glucose homeostasis in vivo Nrf2 suppresses blood glucose levels by protecting pancreatic β cells from oxidative stress and improving peripheral tissue glucose utilization. To elucidate the molecular mechanisms by which Nrf2 contributes to the maintenance of glucose homeostasis, we generated skeletal muscle (SkM)-specific Keap1 knockout (Keap1MuKO) mice that express abundant Nrf2 in their SkM and then examined Nrf2 target gene expre

Oxidative stress is an essential component in the progression of diabetic kidney disease (DKD), and the transcription factor NF-E2-related factor-2 (Nrf2) plays critical roles in protecting the body against oxidative stress. To clarify the roles of Nrf2 in protecting against DKD, in this study we prepared compound mutant mice with diabetes and loss of antioxidative defense. Specifically, we prepared compound Ins2^Akita/+ (Akita) and Nrf2 knockout (Akita::Nrf2^-/-) or Akita an

<b><i>Significance:</i></b> Central nervous system (CNS) diseases are disorders of the brain and/or spinal cord and include neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and multiple sclerosis. Nuclear factor erythroid 2-related factor 2 (NRF2) is a transcription factor belonging to the cap-n-collar family that harbors a unique basic leucine zipper motif and plays as a master regulator of homeostatic responses. <b><i>Recent Advances:</i></b> Kelch-like ECH-associat

ATRA increases NO production by eNOS phosphorylation through RAR-mediated PI3K/Akt pathway activation in vascular ECs and possibly plays beneficial roles in vascular endothelium. Retinoids may therefore be candidates as novel therapeutic agents against vascular disorders with endothelial damage.

Transcription factor Nrf2 (nuclear factor E2-related factor 2) is a master regulator of cellular defense system against oxidative and electrophilic stresses and is negatively regulated by an adaptor protein Keap1 (Kelch-like ECH-associated protein 1). Nrf2 also plays a pivotal role in metabolic homeostasis, such as lipid metabolism and energy expenditure as well as redox homeostasis. FGF21 (fibroblast growth factor 21) is known as a key mediator of glucose and lipid metabolism. Here, we found th

Peroxisome proliferator-activated receptor-γ (PPARγ) is a nuclear receptor for the antidiabetic agent thiazolidinedione, which exerts various physiological activities, independent of lowering blood glucose. However, the role of PPARγ in aldosterone production has not been clarified. The objective of this study was to investigate the effect of PPARγ on aldosterone synthase gene (CYP11B2) expression and aldosterone production. Localization of PPARγ expression in normal adrenal cortex was determine

Hepatocyte growth factor (HGF) has recently been the focus of attention due to its angiogenic effects, which are similar to those of vascular endothelial growth factor (VEGF); because of these effects, HGF is considered to be a novel therapeutic agent against vascular disorders, including atherosclerotic angiopathies. Although nitric oxide (NO), which is derived from vascular endothelial cells (ECs), is also involved in angiogenesis, little is known regarding the interactions between HGF and NO.

Nrf1 (NF-E2-related factor 1) is a basic region leucine zipper-type transcription factor belonging to the CNC (cap-'n'-collar) family. Major pathophysiological contribution of Nrf1 remains unclear. As single nucleotide polymorphism rs3764400 in 5'-flanking region of NRF1 gene appears to associate with obesity, in this study, we focused on the Nrf1 function on metabolism. We found that the risk C allele of rs3764400 increased NRF1 gene transcriptional activity compared with the T allele in hepato

ATRA and a synthetic RAR agonist tamibarotene (Am80) induce granulocytic differentiation of human acute leukemia HL-60 cells and have been used in antineoplastic therapy. ATRA induces CD38 antigen during HL-60 cell differentiation, which interacts with CD31 antigen on the vascular EC surface and may induce disadvantages in the therapy. We here examined the mechanisms of the ATRA-mediated CD38 induction and compared the difference between ATRA- and tamibarotene-mediated induction. Tamibarotene-in