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Transcription factor ddi

Nicolas J Lehrbach, Gary Ruvkun
Proteasomes are essential for protein homeostasis in eukaryotes. To preserve cellular function, transcription of proteasome subunit genes is induced in response to proteasome dysfunction caused by pathogen attacks or proteasome inhibitor drugs. In Caenorhabditis elegans, this response requires SKN-1, a transcription factor related to mammalian Nrf1/2. Here, we use comprehensive genetic analyses to identify the pathway required for C. elegans to detect proteasome dysfunction and activate SKN-1. Genes required for SKN-1 activation encode regulators of ER traffic, a peptide N-glycanase, and DDI-1, a conserved aspartic protease...
August 16, 2016: ELife
Jérôme Tourret, Gilbert Deray, Corinne Isnard-Bagnis
Tenofovir disoproxil fumarate (TDF), the first nucleotidic inhibitor of HIV reverse transcription, became available in 2001. It has been extensively used worldwide and is now the most prescribed antiretroviral (ARV) drug. Its high antiviral activity and favorable metabolic profile are responsible for its success. Furthermore, TDF has been associated with other ARVs to form new combined antiretroviral treatments in only one tablet once-a-day, which increases treatment adherence. Fears of potential nephrotoxicity that tenofovir would have in common with two other drugs from the same family (adefovir, used to treat hepatitis B, and cidofovir, used to treat cytomegalovirus infections) were alleviated by the early clinical trials...
October 2013: Journal of the American Society of Nephrology: JASN
Bing-fang Hu, Hui-chang Bi, Min Huang
Nuclear receptors pregnane X receptor (PXR) and constitutive androstane receptor (CAR) are originally characterized as transcription factors regulating many target genes. Recent works have revealed that these nuclear receptors play critical roles in regulating genes that encode drug metabolism enzymes and modulating hepatic energy metabolism, such as down-regulating gluconeogenesis, fatty acid oxidation, and ketogenesis, as well as up-regulating lipogenesis. Studies on PXR and CAR have important implication on drug-drug interaction (DDI) and potential disease treatment targets...
October 2011: Yao Xue Xue Bao, Acta Pharmaceutica Sinica
Amin R Mazloom, Ruth Dannenfelser, Neil R Clark, Arsen V Grigoryan, Kathryn M Linder, Timothy J Cardozo, Julia C Bond, Aislyn D W Boran, Ravi Iyengar, Anna Malovannaya, Rainer B Lanz, Avi Ma'ayan
Coregulator proteins (CoRegs) are part of multi-protein complexes that transiently assemble with transcription factors and chromatin modifiers to regulate gene expression. In this study we analyzed data from 3,290 immuno-precipitations (IP) followed by mass spectrometry (MS) applied to human cell lines aimed at identifying CoRegs complexes. Using the semi-quantitative spectral counts, we scored binary protein-protein and domain-domain associations with several equations. Unlike previous applications, our methods scored prey-prey protein-protein interactions regardless of the baits used...
December 2011: PLoS Computational Biology
Yongmin Liu, Phuonggiang Nguyen, Tara Z Baris, Miriam C Poirier
Despite the highly effective impact of NRTI therapy in patients infected with the human immunodeficiency virus type 1 (HIV-1), long-term treatment has revealed cardiotoxicity, considered to be due to mitochondrial dysfunction. To evaluate mitochondrial damage, and design therapeutic interventions, we established cultures of rat H9c2 and mouse HL-1 cardiomyocytes and exposed them to the NRTIs zidovudine (AZT), and AZT plus didanosine (ddI). Proliferation assays showed that H9c2 cells grew well in 50 μM AZT and 50 μM AZT/50 μM ddI and that HL-1 cells grew well in 10 μM AZT and 10 μM AZT/10 μM ddI...
June 2012: Cardiovascular Toxicology
Bhuvana A Setty, Karen C Hayani, Bruce I Sharon, Mary Lou Schmidt
A 15-year-old male with congenital HIV infection was diagnosed with chronic myelogenous leukemia (CML) at age 4 years 9 months. HIV was initially treated with zidovudine. For the last >10 years he has received didanosine, lamivudine, and nelfinavir. CML was treated with Interferon alfa (INF-alpha) for >10 years and a brief course of hydroxyurea (HU). He remained in chronic phase CML since diagnosis however recent molecular monitoring revealed increased BCR/ABL transcripts necessitating a change in therapy to imatinib...
October 2009: Pediatric Blood & Cancer
Raphael M Oguariri, Terrence W Brann, Tomozumi Imamichi
The existence of viral latency limits the success of highly active antiretroviral therapy. With the therapeutic intention of reactivating latent virus to induce a cure, in this study we assessed the impact of cell synchronizers on HIV gene activation in latently infected U1 cells and investigated the molecular mechanisms responsible for such effect. Latently infected U1 cells were treated with 10 drugs including hydroxyurea (HU) and HIV-1 replication monitored using a p24 antigen capture assay. We found that HU was able to induce HIV-1 replication by 5-fold...
February 9, 2007: Journal of Biological Chemistry
M Luisa Rodríguez de la Concepción, Pilar Yubero, Joan C Domingo, Roser Iglesias, Pere Domingo, Frcancesc Villarroya, Marta Giralt
OBJECTIVE: Human adipose depots contain remnant brown adipocytes interspersed among white adipocytes, and disturbances of brown with respect to white adipocyte biology have been implicated in highly active antiretroviral therapy (HAART)-induced lipomatosis. Brown adipocytes express the uncoupling protein-1 (UCP1) and contain a large number of mitochondria, potential targets of HAART toxicity. The aim of this study was to evaluate the effects of reverse transcriptase inhibitors (RTIs) on primary brown adipocytes differentiated in culture...
2005: Antiviral Therapy
Candan Depboylu, Todd A Reinhart, Osamu Takikawa, Yoshinori Imai, Hitomi Maeda, Hiroaki Mitsuya, Dianne Rausch, Lee E Eiden, Eberhard Weihe
Increased kynurenine pathway metabolism has been implicated in the aetiology of lentiviral encephalopathy. Indoleamine-2,3-dioxygenase (IDO) initiates the increased production of kynurenine pathway metabolites like quinolinic acid (QUIN). QUIN itself is elevated in AIDS-diseased monkey and human brain parenchyma and cerebrospinal fluid at levels excitotoxic for neurons in vitro. This study investigates the cellular origin of IDO biosynthesis in the brain of rhesus monkeys infected with simian immunodeficiency virus (SIV) and explores the effects of CNS-permeant antiretroviral treatment...
June 2004: European Journal of Neuroscience
E Ravot, J Lisziewicz, F Lori
The tenacious effort to develop new, specific agents to treat HIV infection is currently accompanied by a reconsideration of existing drugs on the basis of their known or putative effects on the retroviral life cycle and/or the tuning of immune mechanisms. Three specific 'older' compounds that interfere with HIV infection by both a direct antiviral activity, and a modulation of T-cell activation and proliferation have received the most attention. Hydroxurea, a classical chemotherapeutic agent, inhibits retroviral reverse transcription by targeting a cellular enzyme responsible for the synthesis of deoxynucleoside triphosphates...
December 1999: Drugs
D Freyssenet, M DiCarlo, P Escobar, J Grey, J Schneider, D A Hood
Zidovudine (AZT) and didanosine (ddI), two drugs used in the treatment of AIDS, are also known to cause mitochondrial abnormalities. We investigated the physiological relevance of the mitochondrial defects by measuring in situ skeletal muscle performance and cytochrome c oxidase (CYTOX) enzyme activity in heart muscle, red highoxidative (RG) and white low-oxidative (WG) portions of the gastrocnemius muscle of control (n = 17), AZT-(n = 14), or ddI-treated (n = 11) rats for 28 days. We also evaluated the hypothesis that AZT treatment could alter the expression of the mitochondrial transcription factor A (mtTFA), a key molecule involved in mitochondrial DNA (mtDNA) replication and transcription...
January 1999: Canadian Journal of Physiology and Pharmacology
M S Sheikh, E Fernandez-Salas, M Yu, A Hussain, J D Dinman, S W Peltz, Y Huang, A J Fornace
We report the cloning and characterization of a DNA damage-inducible (DDI) transcript DDI A121. The full-length human DDI A121 cDNA contains an open reading frame of 113 amino acids, corresponding to a protein of 12.7 kDa. The deduced amino acid sequence of A121 shows high homology to the yeast translation initiation factor (eIF) sui1 and also exhibits perfect identity to the partial sequence of recently purified human eIF1. Expression of human A121 corrected the mutant sui1 phenotype in yeast, demonstrating that human A121 encodes a bona fide translation initiation factor that is equivalent to yeast sui1p...
June 4, 1999: Journal of Biological Chemistry
M S Sheikh, F Carrier, M A Papathanasiou, M C Hollander, Q Zhan, K Yu, A J Fornace
Low ratio hybridization subtraction technique was previously used in this laboratory to enrich and isolate a number of low abundance UV-inducible hamster transcripts (Fornace, A. J., Jr., Alamo, I. J., and Hollander, M. C. (1988) Proc. Natl. Acad. Sci. U. S. A. 85, 8800-8804) that led to the identification and cloning of five important hamster and human GADD genes (Fornace, A. J., Jr., Nebert, D. W., Hollander, M. C., Luethy, J. D., Papathanasiou, M., Fargnoli, J., and Holbrook, N. J. (1989) Mol. Cell. Biol...
October 17, 1997: Journal of Biological Chemistry
P Bagnarelli, A Valenza, S Menzo, A Manzin, G Scalise, P E Varaldo, M Clementi
The dynamics of viral activity during different phases of human immunodeficiency virus type 1 (HIV-1) infection were investigated by competitive PCR methods. In particular, we studied the time course of three quantitative molecular parameters of viral activity (genomic RNA copy number in plasma and provirus and late HIV-1 transcript molecule copy numbers in peripheral blood CD4+ T lymphocytes) in untreated patients and patients treated with specific anti-HIV-1 compounds. The results shown here indicate that direct RNA parameters are quantitative molecular indices sensitive enough to be used for a more accurate evaluation of the natural history of this infection and that an indirect parameter, the mean transcriptional activity for each provirus in CD4+ T lymphocytes, may be important in studying this infection in vivo at the molecular level...
April 1994: Journal of Virology
S Aoki-Sei, M C O'Brien, H Ford, H Fujii, D A Gilbert, D A Cooney, D G Johns, S Broder, H Mitsuya
Hep G2-derived hepatoblastoma cells (2.2.15), which actively produce hepatitis B virus (HBV), were cultured in the presence of 2',3'-dideoxyguanosine (ddG), 2',3'-dideoxyinosine, or 3'-azido-2',3'-dideoxythymidine (AZT). ddG was the most potent agent. It diminished viral replication by up to 95%, as assessed by the amount of episomal HBV DNA, without impairing cellular growth. AZT was the least effective against HBV. Northern blot analysis revealed no apparent difference in the pregenomic viral RNA profile, suggesting that these dideoxynucleosides suppress reverse transcription in the replicative cycle of HBV...
November 1991: Journal of Infectious Diseases
A J Fornace, J Jackman, M C Hollander, B Hoffman-Liebermann, D A Liebermann
As discussed throughout this paper, many mammalian DDI genes are associated with growth responses, including both positive responses to growth stimulation and negative responses involving transient growth arrest and terminal differentiation. It is interesting that several immediate-early genes encoding transcription factors, the jun genes, are DDI, are induced by terminal differentiation, and also are associated with positive growth responses. In negative growth-response genes, their control is complex and almost certainly involves multiple regulatory mechanisms...
November 21, 1992: Annals of the New York Academy of Sciences
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