Li J.Z.,Blacksburg High School |
Dou X.,Shandong University |
Zhu H.,Campbell University |
Jia Z.,University of North Carolina at Greensboro |
Li Y.,Campbell University
Molecular and Cellular Biochemistry | Year: 2013
Mesalamine (5-aminosalicylic acid, 5-ASA) is known to be the first-line medication for treatment of patients with ulcerative colitis. Studies have demonstrated that ulcerative colitis patients treated with 5-ASA have an overall decrease in the risk of developing colorectal carcinoma. However, the mechanisms underlying 5-ASA-mediated anti-inflammatory and anti-cancer effects are yet to be elucidated. Because peroxynitrite has been critically involved in inflammatory stress and carcinogenesis, this study was undertaken to investigate the effects of 5-ASA in peroxynitrite-induced DNA strand breaks, an important event leading to peroxynitrite-elicited cytotoxicity. Incubation of φX-174 plasmid DNA with the peroxynitrite generator 3-morpholinosydnonimine (SIN-1) led to the formation of both single- and double-stranded DNA breaks in a concentration-dependent manner. The presence of 5-ASA at 0.1 and 1.0 mM was found to significantly inhibit SIN-1-induced DNA strand breaks in a concentrationdependent manner. The consumption of oxygen induced by SIN-1 was found to not be affected by 5-ASA at 0.1-50 mM, indicating that 5-ASA at these concentrations is not involved in the auto-oxidation of SIN-1 to form peroxynitrite. It is observed that 5-ASA at 0.1-1 mM showed considerable inhibition of peroxynitrite-mediated luminol chemiluminescence in a dose-dependent fashion, suggesting that 5-ASA is able to directly scavenge the peroxynitrite. Electron paramagnetic resonance (EPR) spectroscopy in combination with spin-trapping experiments, using 5,5- dimethylpyrroline-N-oxide (DMPO) as spin trap resulting in the formation of DMPO-hydroxyl radical adduct from peroxynitrite, and 5-ASA only at higher concentration (1 mM) inhibited the hydroxyl radical adduct while shifting EPR spectra, indicating that 5-ASA at higher concentrations may generate a more stable free radical species rather than acting purely as a hydroxyl radical scavenger. Taken together, these studies demonstrate for the first time that 5-ASA can potently inhibit peroxynitrite-mediated DNA strand breakage, scavenge peroxynitrite, and affect peroxynitrite-mediated radical formation, which may be responsible, at least partially, for its anti-inflammatory and anti-cancer effects.
Rosen R.,West Virginia University |
Swiggum J.,West Virginia University |
McLaughlin M.A.,West Virginia University |
Lorimer D.R.,West Virginia University |
And 67 more authors.
Astrophysical Journal | Year: 2013
We present the discovery and timing solutions of five new pulsars by students involved in the Pulsar Search Collaboratory, a NSF-funded joint program between the National Radio Astronomy Observatory and West Virginia University designed to excite and engage high-school students in Science, Technology, Engineering, and Mathematics (STEM) and related fields. We encourage students to pursue STEM fields by apprenticing them within a professional scientific community doing cutting edge research, specifically by teaching them to search for pulsars. The students are analyzing 300 hr of drift-scan survey data taken with the Green Bank Telescope at 350 MHz. These data cover 2876 deg2 of the sky. Over the course of five years, more than 700 students have inspected diagnostic plots through a web-based graphical interface designed for this project. The five pulsars discovered in the data have spin periods ranging from 3.1 ms to 4.8 s. Among the new discoveries are PSR J1926-1314, a long period, nulling pulsar; PSR J1821+0155, an isolated, partially recycled 33 ms pulsar; and PSR J1400-1438, a millisecond pulsar in a 9.5 day orbit whose companion is likely a white dwarf star. © 2013. The American Astronomical Society. All rights reserved.