Arnt rolf

The human aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that is a pivotal regulator of human physiology and pathophysiology. Allosteric inhibition of AhR was previously thought to be untenable. Here, we identify carvones as noncompetitive, insurmountable antagonists of AhR and characterize the structural and functional consequences of their binding. Carvones do not displace radiolabeled ligands from binding to AhR but instead bind allosterically within the bHLH/PAS-A region of AhR...

The aryl hydrocarbon receptor (AHR) is a ligand-dependent transcription factor regulating adaptive and maladaptive responses toward exogenous and endogenous signals. Research from various biomedical disciplines has provided compelling evidence that the AHR is critically involved in the pathogenesis of a variety of diseases and disorders, including autoimmunity, inflammatory diseases, endocrine disruption, premature aging and cancer. Accordingly, AHR is considered an attractive target for the development of novel preventive and therapeutic measures...

BACKGROUND AND PURPOSE: To compare early side effects and patient compliance of accelerated partial breast irradiation (APBI) with multicatheter brachytherapy to external beam whole breast irradiation (WBI) in a low-risk group of patients with breast cancer. MATERIAL AND METHODS: Between April 2004 and July 2009, 1328 patients with UICC stage 0-IIA breast cancer were randomized to receive WBI with 50Gy and a boost of 10Gy or APBI with either 32.0Gy/8 fractions, or 30...

Recent candidate gene studies using a human liver bank and in vivo validation in healthy volunteers identified polymorphisms in cytochrome P450 (CYP) 3A4 gene (CYP3A4*22), Ah-receptor nuclear translocator (ARNT), and peroxisome proliferator-activated receptor-α (PPAR-α) genes that are associated with the CYP3A4 phenotype. We hypothesized that the variants identified in these genes may be associated with altered clopidogrel response, since generation of clopidogrel active metabolite is, partially mediated by CYP3A activity...

BACKGROUND: No previous in vitro studies have tested radio frequency radiation for at least one full cell cycle in culture. The aim was to test if exposure used in mobile phones and wireless network technologies would induce DNA damage in cultured human lymphocytes with and without a known clastogen. MATERIALS AND METHODS: Lymphocytes from six donors were exposed to 2.3 GHz, 10 W/m(2) continuous waves, or 2.3 GHz, 10 W/m(2) pulsed waves (200 Hz pulse frequency, 50% duty cycle)...

BACKGROUND: There are few cell studies on the direct genotoxic effects of microwave radiation. In this study, cytogenetic effects of microwave radiation alone or in combination with mitomycin C (MMC) were investigated. MATERIALS AND METHODS: Lymphocytes from two smoking and four non-smoking donors were exposed for 53 hours in vitro to 1.0 W/m(2) continuous-wave radiation at 18.0 GHz or 10 W/m(2) pulsed-wave at 16.5 GHz, alone or in combination with MMC. DNA synthesis and repair were inhibited in vitro in some cultures...

PURPOSE: To evaluate the efficacy of simultaneous postoperative temozolomide radiochemotherapy in glioblastoma patients. PATIENTS AND METHODS: From February 2002 to July 2004, n = 65 patients from 11 German centers with macroscopic complete tumor resection were randomized to receive either postoperative radiotherapy alone (RT, n = 35) or postoperative radiotherapy with simultaneous temozolomide (RT + TMZ, n = 30). Patients were stratified according to age (< or =/>50 years) and WHO performance score (0-1 vs...

A growing family of helix-loop-helix PAS (HLH-PAS) transcription factors has emerged recently. These proteins form heterodimers and are involved in adaptation to environmental or physiologic stresses as well as in embryonic development. We describe the cloning and characterization of a novel HLH-PAS protein termed LE-PAS (limbic-enriched PAS) in mouse. LE-PAS consists of 802 amino acids and has a predicted molecular mass of 87.4 kDa. In adult mice, it is expressed exclusively in brain. Northern blot and in situ hybridization analysis indicate that LE-PAS is expressed in the limbic system and olfactory bulb...

Transferrin (Tf) is a liver-derived iron transport protein whose plasma concentration increases following exposure to hypoxia. Here, we present a cell culture model capable of expressing Tf mRNA in an oxygen-dependent manner. A 4-kilobase pair Tf promoter/enhancer fragment as well as the 300-base pair liver-specific Tf enhancer alone conveyed hypoxia responsiveness to a heterologous reporter gene construct in hepatoma but not HeLa cells. Within this enhancer, a 32-base pair hypoxia-responsive element was identified, which contained two hypoxia-inducible factor-1 (HIF-1) binding sites (HBSs)...

The discovery that the oxygen-regulated transcription factor HIF-1 alpha and the dioxin receptor AhR share the common heterodimerization partner ARNT (HIF-1 beta) raised the question whether a cross-talk between oxygen and dioxin signal transduction pathways exists. To answer this question we investigated an ARNT-deficient mutant cell line (Hepa1C4), which has lost its capability of responding to dioxin. The results demonstrate that the presence of ARNT is indispensable for hypoxia-inducible HIF-1 DNA binding as well as for oxygen-regulated reporter gene activity mediated by the EPO 3' hypoxia response element (HRE)...