Zidovudine

Publication Title: 
Nucleic Acids Research

The ribonucleoprotein enzyme telomerase is a specialized type of cellular reverse transcriptase which synthesizes one strand of telomeric DNA, using as the template a sequence in the RNA moiety of telomerase. We analyzed the effects of various nucleoside analogs, known to be chain-terminating inhibitors of retroviral reverse transcriptases, on Tetrahymena thermophila telomerase activity in vitro. We also analyzed the effects of such analogs on telomere length and maintenance in vivo, and on vegetative growth and mating of Tetrahymena cells.

Author(s): 
Strahl, C.
Blackburn, E. H.
Publication Title: 
Molecular and Cellular Biology

The ribonucleoprotein telomerase, a specialized cellular reverse transcriptase, synthesizes one strand of the telomeric DNA of eukaryotes. We analyzed telomere maintenance in two immortalized human cell lines: the B-cell line JY616 and the T-cell line Jurkat E6-1, and determined whether known inhibitors of retroviral reverse transcriptases could perturb telomere lengths and growth rates of these cells in culture. Dideoxyguanosine (ddG) caused reproducible, progressive telomere shortening over several weeks of passaging, after which the telomeres stabilized and remained short.

Author(s): 
Strahl, C.
Blackburn, E. H.
Publication Title: 
Nucleic Acids Research

The ribonucleoprotein enzyme telomerase is a specialized type of cellular reverse transcriptase which synthesizes one strand of telomeric DNA, using as the template a sequence in the RNA moiety of telomerase. We analyzed the effects of various nucleoside analogs, known to be chain-terminating inhibitors of retroviral reverse transcriptases, on Tetrahymena thermophila telomerase activity in vitro. We also analyzed the effects of such analogs on telomere length and maintenance in vivo, and on vegetative growth and mating of Tetrahymena cells.

Author(s): 
Strahl, C.
Blackburn, E. H.
Publication Title: 
Molecular and Cellular Biology

The ribonucleoprotein telomerase, a specialized cellular reverse transcriptase, synthesizes one strand of the telomeric DNA of eukaryotes. We analyzed telomere maintenance in two immortalized human cell lines: the B-cell line JY616 and the T-cell line Jurkat E6-1, and determined whether known inhibitors of retroviral reverse transcriptases could perturb telomere lengths and growth rates of these cells in culture. Dideoxyguanosine (ddG) caused reproducible, progressive telomere shortening over several weeks of passaging, after which the telomeres stabilized and remained short.

Author(s): 
Strahl, C.
Blackburn, E. H.
Publication Title: 
Molecules (Basel, Switzerland)

Gossypol, the polyphenolic constituent isolated from cottonseeds, has been used as a male antifertility drug for a long time, and has been demonstrated to exhibit excellent anti-tumor activity towards multiple cancer types. The toxic effects of gossypol limit its clinical utilization, and enzyme inhibition is an important facet of this. In the present study, in vitro human liver microsomal incubation system supplemented with UDPGA was used to investigate the inhibition of gossypol towards UGT1A1, 1A9 and 2B7-mediated metabolism of xenobiotics and endogenous substances.

Author(s): 
Zhang, Yong-sheng
Yuan, Jun
Fang, Zhong-Ze
Tu, Yan-yang
Hu, Cui-Min
Li, Gan
Wang, Liang
Deng, Jian-Ping
Yao, Jia-Jiu
Li, Hai-Rong
Publication Title: 
Drug Metabolism and Disposition: The Biological Fate of Chemicals

UDP-glucuronosyltransferase 2B7 (UGT2B7) is involved in the glucuronidation of a wide array of clinically important drugs and endogenous compounds in humans. The aim of this study was to identify an isoform-selective probe substrate that could be used to investigate genetic and environmental influences on glucuronidation mediated by UGT2B7. Three potential probe substrates [3'-azido-3'-deoxythymidine (AZT), morphine, and codeine], were evaluated using recombinant UGTs and human liver microsomes (HLMs; n = 54).

Author(s): 
Court, Michael H.
Krishnaswamy, Soundarajan
Hao, Qin
Duan, Su X.
Patten, Christopher J.
von Moltke, Lisa L.
Greenblatt, David J.
Publication Title: 
The Journal of Antimicrobial Chemotherapy

BACKGROUND: Switching a thymidine analogue to a non-thymidine analogue or changing to a nucleoside-sparing regimen has been shown to partially reverse peripheral lipoatrophy. The current study evaluated both approaches.

Author(s): 
Tebas, P.
Zhang, J.
Häfner, R.
Tashima, K.
Shevitz, A.
Yarasheski, K.
Berzins, B.
Owens, S.
Forand, J.
Evans, S.
Murphy, R.
Publication Title: 
Cardiovascular Toxicology

Cardiovascular effects of chronic AZT treatment on SD male rats (185 g) fed either a normal Mg diet (0.1% MgO) or a high Mg diet (0.6% MgO) were examined. AZT treatment (1 mg/ml drinking water) for 3 weeks led to a 5.5-fold (0.88 +/- 0.11 nmol/min/10(6) cells, P < 0.05) elevation in neutrophil basal activity of O2(-) production versus controls (0.16 +/- 0.03 nmol/min, assayed ex vivo as SOD-inhibitable cytochrome c reduction).

Author(s): 
Mak, I. Tong
Chmielinska, Joanna J.
Kramer, Jay H.
Weglicki, William B.
Publication Title: 
HIV clinical trials

PURPOSE: Oxidant stress may be an effect of antiretroviral therapy (ART) or chronic HIV infection. Plasma F2-isoprostanes (F2-IsoP) reflect lipid peroxidation and oxidant stress and have been described in ART-associated toxicities. We explored factors associated with F2-IsoP in HIV-infected adults. METHODS: HIV-infected adults enrolled in this cross-sectional study were (a) on ART including zidovudine or stavudine but not non-nucleoside reverse transcriptase inhibitors (NNRTI), (b) on ART including NNRTI, or (c) not on ART.

Author(s): 
Redhage, Leigh Anne
Shintani, Ayumi
Haas, David W.
Emeagwali, Nkiruka
Markovic, Milica
Oboho, Ikwo
Mwenya, Christopher
Erdem, Husamettin
Acosta, Edward P.
Morrow, Jason D.
Hulgan, Todd
Publication Title: 
Laboratory Investigation; a Journal of Technical Methods and Pathology

Thymidylate kinase (TMPK) is a nucleoside monophosphate kinase that catalyzes phosphorylation of thymidine monophosphate to thymidine diphosphate. TMPK also mediates phosphorylation of monophosphates of thymidine nucleoside analog (NA) prodrugs on the pathway to their active triphosphate antiviral or antitumor moieties. Novel transgenic mice (TG) expressing human (h) TMPK were genetically engineered using the alpha-myosin heavy chain promoter to drive its cardiac-targeted overexpression.

Author(s): 
Kohler, James J.
Hosseini, Seyed H.
Cucoranu, Ioan
Zhelyabovska, Olga
Green, Elgin
Ivey, Kristopher
Abuin, Allison
Fields, Earl
Hoying, Amy
Russ, Rodney
Santoianni, Robert
Raper, C. Michael
Yang, Qinglin
Lavie, Arnon
Lewis, William

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