Browsing by Subject "Hydrogen peroxide"
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Item ATM activation by oxidative stress(2009-08) Guo, Zhi, 1978-; Paull, Tanya T.The Ataxia-telangiectasia mutated (ATM) protein is regarded as the major regulator of the cellular response to DNA double Strand Breaks (DSBs). In response to DSBs, ATM dimers dissociates into active monomers in a process promoted by Mre11-Rad50-Nbs1 (MRN) complex. ATM-deficient cells exhibit signs of chronic oxidative stress, suggesting that ATM plays an important role in the regulation of reactive oxygen species (ROS). I show for the first time that ATM can be activated by oxidative stress directly in the form of exposure to H₂O₂. In vitro kinase assays with purified ATM suggest that the activation by H₂O₂ is independent of DSBs and the MRN complex. In 293T cells, H₂O₂ induces ATM autophosphorylation on serine 1981. p53 and Chk2 are also phosphorylated by ATM after H₂O₂ treatment but not histone H2AX and heterochromatin protein Kap1, indicating that ATM activation by H₂O₂ in human cells is independent of DNA damage. I also show that the cysteine residue 2991 is critical for ATM activation by H₂O₂ in vitro.Item Determination of trace levels of aqueous and gas phase hydrogen peroxide(Texas Tech University, 1985-05) Hwang, Hoon.Item The effects of polymicrobial metabolism on pathogenesis and survival in Aggregatibacter actinomycetemcomitans(2011-08) Ramsey, Matthew M.; Whiteley, Marvin; Marcotte, Edward; Meyer, Richard; Trent, Stephen M.; Walker, JamesIn this dissertation I describe a model system to characterize the response of an oral bacterial pathogen, Aggregatibacter actinomycetemcomitans to the metabolic byproducts of a representative member of the oral flora, Streptococcus gordonii. A. actinomycetemcomitans is a causative agent of periodontal infections in humans. To cause infection, A. actinomycetemcomitans must overcome numerous challenges, including the host immune system and toxic metabolite production from other microbes. The most numerically dominant flora in the oral cavity are oral streptococci, which are well known for their ability to produce copious amounts of lactic acid and H₂O₂. By studying the response to H₂O₂ and lactic acid in pure and co-cultures, I have demonstrated that A. actinomycetemcomitans responds to these metabolites by several novel mechanisms that both enhance its survival in the presence of the host immune system and in the presence of the model oral streptococci S. gordonii. These studies have demonstrated that metabolites produced by normal flora can impact the survival of a single species in vivo as much as previously known virulence factors have done. In addition, I present a new method for measuring metabolite production in an attached cell population. This method is a novel application of scanning electrochemical microscopy (SECM) and I used this technique to study H₂O₂ production in the three dimensional space surrounding a multispecies biofilm in real time. In a related study I present the use of SECM to discover a novel redox chemistry phenomenon in the opportunistic pathogen Pseudomonas aeruginosa.