Hypersensitive site 2 located in the beta-globin locus control region confers high levels of expression to genes cluster. A tandem repeat consensus sequence for transcription factors AP1 and NF-E2 (activating protein 1 nuclear factor erythroid 2, respectively) is present within hypersensitive absolutely required strong enhancer activity. This binds, vitro vivo, ubiquitous proteins family recently cloned erythroid-specific NF-E2. Using as a recognition probe screen lambda gt11 cDNA library...

The antioxidant responsive element (ARE) mediates transcriptional regulation of phase II detoxification enzymes and proteins such as NAD(P)H:quinone oxidoreductase (NQO1), glutathione S-transferases, glutamate-cysteine ligase. In this study, we demonstrate that NF-E2-related factor-2 (Nrf2) plays a major role in activation ARE-driven genes identify Nrf2-dependent by oligonucleotide microarray analysis using primary cortical astrocytes from Nrf2(+/+) Nrf2(-/-) mice. had decreased basal NQO1...

Nrf2, a member of the “cap ‘n collar” group transcription factors, is important for protecting cells against oxidative damage. We investigated its role in detoxification acetaminophen [ N -acetyl- p -aminophenol (APAP)]-induced hepatotoxicity. When Nrf2 knockout (Nrf2 −/− ) and wild-type mice were given APAP by i.p. injection, highly susceptible to treatment. With doses that tolerated mice, died liver failure. hepatic glutathione was depleted after dose 400 mg/kg APAP, able compensate regain...

The locus control region of the β-globin gene is composed four erythroid-specific hypersensitive sites. Hypersensitive site 2 has been shown to be a powerful enhancer and contains tandem repeat sequence for transcription factors AP1 NFE2 (activating protein 1 nuclear factor erythroid 2, respectively). human NRF2 (NFE2 related 2) isolated by bacterial expression screening using this core as probe. p45-NFE2, NRF1, belong CNC (“cap ‘n’ collar”) subfamily basic region–leucine zipper factors,...

Nrf2 is a member of the “cap ‘n’ collar” family transcription factors. These factors bind to NF-E2 binding sites (GCTGAGTCA) that are essential for regulation erythroid-specific genes. expressed in wide range tissues, many which expression phase 2 detoxification −/− mice viable and have normal phenotype under laboratory conditions. The site subset antioxidant response elements sequence GCNNNGTCA. regulatory sequences found on promoters several genes inducible by xenobiotics antioxidants. We...

Oxidative stress has been implicated in the etiology of Parkinson's disease (PD) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) animal model PD. It is known that under conditions oxidative stress, transcription factor NF-E2-related (Nrf2) binds to antioxidant response element (ARE) induce phase II detoxification enzymes. To investigate role Nrf2 process MPTP-induced toxicity, mice expressing human placental alkaline phosphatase (hPAP) gene driven by a promoter containing core ARE...

The development of retroviral vectors that target specific cell types could have important implications for the design gene therapy strategies. A chimeric protein containing polypeptide hormone erythropoietin and part env ecotropic Moloney murine leukemia virus was engineered into virus. This became several times more infectious cells bearing receptor, it also human receptor. type tissue-specific targeting by means ligand-receptor interactions may broad applications to a variety delivery systems.

Keratinocyte growth factor (KGF) is a potent mitogen for epithelial cells, and it promotes survival of these cells under stress conditions. In search KGF-regulated genes in keratinocytes, we identified the gene encoding transcription NF-E2-related 2 (Nrf2). Nrf2 key player cellular response. This might be particular importance during wound healing, where large amounts reactive oxygen species are produced as defense against invading bacteria. Therefore, studied repair process knockout mice....

β-thalassemia, one of the most common genetic diseases worldwide, is caused by mutations in human hemoglobin beta ( HBB ) gene. Creation induced pluripotent stem cells (iPSCs) from β-thalassemia patients could offer an approach to cure this disease. Correction disease-causing iPSCs restore normal function and provide a rich source for transplantation. In study, we used latest gene-editing tool, CRISPR/Cas9 technology, combined with piggyBac transposon efficiently correct patient-derived...

Individuals homozygous for the C-C chemokine receptor type 5 gene with 32-bp deletions (CCR5Δ32) are resistant to HIV-1 infection. In this study, we generated induced pluripotent stem cells (iPSCs) naturally occurring CCR5Δ32 mutation through genome editing of wild-type iPSCs using a combination transcription activator-like effector nucleases (TALENs) or RNA-guided clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 together piggyBac technology. Remarkably, TALENs...

<h3>OBJECTIVE</h3> To evaluate the use of cardiac troponin I (cTnI), creatine kinase-MB_mass (CK-MB_mass), myosin light chain 1 (MLC 1), and myoglobin in identifying "high risk" patients with chest pain who will experience serious events (SCEs) hospital. <h3>DESIGN</h3> Prospective study. <h3>SETTING</h3> University affiliated medical centre Philadelphia, USA. <h3>PATIENTS</h3> 208 pain, at &gt; 7% risk acute myocardial infarction (MI), but without new ST segment...

Significance We designed this study to elevate fetal hemoglobin for the treatment of β-thalassemia and sickle cell disease (SCD). It has long been known that some individuals who are compound heterozygotes or SCD with deletional hereditary persistence (HPFH) have minimal hematological abnormalities mild clinical manifestation compared homozygous patients. used CRISPR-Cas9 modify normal bone marrow hematopoietic stem progenitor cells (HSPCs) HPFH genotype. The erythroid derived from such...

We have devised a complementation assay in yeast to clone mammalian transcriptional activators and used it identify human basic leucine-zipper transcription factor that we designated Nrf1 for NF-E2-related 1. potentially encodes 742-aa protein displays marked homology the mouse NF-E2 factors. activates via binding sites cells. The ubiquitous expression pattern of range promoters containing motif suggest this gene may play role regulation heme synthesis ferritin genes.

The alpha-thalassemia-2 (alpha-thal-2) genotype or mild alpha-thalassemia gene consists of a single structural alpha-globin on the chromosome that normally bears two genes. We used blot hybridization to investigate variation in molecular organization this and determine distributions these variations world population. Two different patterns responsible for alpha-thal-2 were found: first was result 4.2-kilobase pair deletion involving normal 5' (leftward genotype), second probably crossover...

Complex II inhibitors 3-nitropropionic acid (3NP) and malonate cause striatal damage reminiscent of Huntington's disease have been shown to involve oxidative stress in their pathogenesis. Because nuclear factor erythroid 2-related 2 (Nrf2)-dependent transcriptional activation by means the antioxidant response element is known coordinate up-regulation cytoprotective genes involved combating stress, we investigated significance Nrf2 complex II-induced toxicity. We found that Nrf2-deficient...

We studied 47 patients with sickle-cell anemia to determine the effect of alpha-thalassemia on severity their hemolytic anemia. diagnosed objectively by using alpha-globin-gene mapping detect deletions, studying 25 subjects normal four alpha-globin-genes, 18 three, and two. The mean hemoglobin, hematocrit, absolute reticulocyte levels (+/- S.D.) were 7.9 +/- 0.9 g per deciliter (4.9 0.6 mmol liter), 22.9 2.9 cent, 501,000 126,000 cubic millimeter, respectively, in non-thalassemic group; 9.8...

A rapid gene-mapping system uses a high-resolution, dual-laser sorter to identify genes from separate human chromosomes prepared with new stain combination. This was used sort 21 unique chromosome types onto nitrocellulose filter papers. Several labeled gene probes hybridized the sorted chromosomal DNA predicted by their previous assignments. The skeletal muscle glycogen phosphorylase then mapped portion of 11 spot blotting normal and translocated chromosomes.