Abstract

Nitric oxide (NO) is a diatomic radical which can diffuse readily across biological membranes. NO controls and influences a number of critical physiological processes. The best characterized examples of physiological responses controlled by NO include vasodilation and regulation of normal vascular tone, inhibition of platelet aggregation, neuronal transmission and cytostasis. One proposed cellular target for NO which could mediate such cytostatic effects is ribonucleotide reductase (RNR). NO would also be expected to influence related proteins such thioredoxin and thioredoxin reductase. Inhibition of these proteins would also be expected to induce cytostasis. The inhibition of DNA synthesis in target cells has been reported, however, the mechanism of the inhibition is unknown. The goal of the proposed studies, therefore, is to determine the molecular' mechanism of NO inhibition of E. coli ribonucleotide reductase (RNR) and the effect on NO on related proteins. The studies will use cloned and expressed sources of the proteins to address the following specific aims: (l) the effect of NO on thioredoxin (Trx) and thioredoxin reductase (TR), (2) the effect of NO on enzymatic turnover of RNR, (3) the effect of NO on the assembly of the iron center of RNR.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
2P01CA026731-20
Application #
6102035
Study Section
Project Start
1999-03-31
Project End
1999-12-31
Budget Start
1998-10-01
Budget End
1999-09-30
Support Year
20
Fiscal Year
1999
Total Cost
Indirect Cost

  Institution

Name
Massachusetts Institute of Technology
Department
Type
DUNS #
City
Cambridge
State
MA
Country
United States
Zip Code
02139

  Publications

Tajai, Preechaya; Fedeles, Bogdan I; Suriyo, Tawit et al. (2018) An engineered cell line lacking OGG1 and MUTYH glycosylases implicates the accumulation of genomic 8-oxoguanine as the basis for paraquat mutagenicity. Free Radic Biol Med 116:64-72
Rothenberg, Daniel A; Taliaferro, J Matthew; Huber, Sabrina M et al. (2018) A Proteomics Approach to Profiling the Temporal Translational Response to Stress and Growth. iScience 9:367-381
Wang, Xin; Garcia, Carlos T; Gong, Guanyu et al. (2018) Automated Online Solid-Phase Derivatization for Sensitive Quantification of Endogenous S-Nitrosoglutathione and Rapid Capture of Other Low-Molecular-Mass S-Nitrosothiols. Anal Chem 90:1967-1975
Chan, Cheryl; Pham, Phuong; Dedon, Peter C et al. (2018) Lifestyle modifications: coordinating the tRNA epitranscriptome with codon bias to adapt translation during stress responses. Genome Biol 19:228
Gu, Chen; Ramos, Jillian; Begley, Ulrike et al. (2018) Phosphorylation of human TRM9L integrates multiple stress-signaling pathways for tumor growth suppression. Sci Adv 4:eaas9184
Wadduwage, Dushan N; Kay, Jennifer; Singh, Vijay Raj et al. (2018) Automated fluorescence intensity and gradient analysis enables detection of rare fluorescent mutant cells deep within the tissue of RaDR mice. Sci Rep 8:12108
Fedeles, Bogdan I (2017) G-quadruplex-forming promoter sequences enable transcriptional activation in response to oxidative stress. Proc Natl Acad Sci U S A 114:2788-2790
Townsend, Todd A; Parrish, Marcus C; Engelward, Bevin P et al. (2017) The development and validation of EpiComet-Chip, a modified high-throughput comet assay for the assessment of DNA methylation status. Environ Mol Mutagen 58:508-521
Kimoto, Takafumi; Kay, Jennifer E; Li, Na et al. (2017) Recombinant cells in the lung increase with age via de novo recombination events and clonal expansion. Environ Mol Mutagen 58:135-145
Edrissi, Bahar; Taghizadeh, Koli; Moeller, Benjamin C et al. (2017) N6-Formyllysine as a Biomarker of Formaldehyde Exposure: Formation and Loss of N6-Formyllysine in Nasal Epithelium in Long-Term, Low-Dose Inhalation Studies in Rats. Chem Res Toxicol 30:1572-1576

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