A novel thiol oxidation‐based mechanism for adriamycin‐induced cell injury in human macrophages

Asmis, Reto; Wang, Yanmei; Xu, Liang; Kisgati, Marta; Begley, Jim G.; Mieyal, John J.

doi:10.1096/fj.04-2991fje

Cited by 32 publications

(27 citation statements)

References 47 publications

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“…It appears to be a host defense mechanism to protect macrophages against oxidative damages. 28 GLRX was strongly and persistently activated. Also methionine sulfoxide reductase B (MSRB)2 appears to play an important role in repairing oxidative damage to proteins that may occur during infection and it was also upregulated, most prominently at the first time point.…”

Section: Transcriptional Host Response During Tularemia H Andersson Ementioning

confidence: 97%

Transcriptional profiling of the peripheral blood response during tularemia

et al. 2006

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Tularemia is a febrile disease caused by the highly contagious bacterium Francisella tularensis. We undertook an analysis of the transcriptional response in peripheral blood during the course of ulceroglandular tularemia by use of Affymetrix microarrays comprising 14 500 genes. Samples were obtained from seven individuals at five occasions during 2 weeks after the first hospital visit and convalescent samples 3 months later. In total, 265 genes were differentially expressed, 95 of which at more than one time point. The differential expression was verified with real-time quantitative polymerase chain reaction for 36 genes (R 2 ¼ 0.590). The most prominent changes were noted in samples drawn on days 2-3 and a considerable proportion of the upregulated genes appeared to represent an interferon-g-induced response and also a proapoptotic response. Genes involved in the generation of innate and acquired immune responses were found to be downregulated, presumably a pathogen-induced event. A logistic regression analysis revealed that seven genes were good predictors of the early phase of tularemia. This is the first description of the transcriptional host response to ulceroglandular tularemia and the study has identified gene subsets relevant to the pathogenesis of the disease and subsets that may serve as early diagnostic biomarkers.

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Section: Transcriptional Host Response During Tularemia H Andersson Ementioning

confidence: 97%

Transcriptional profiling of the peripheral blood response during tularemia

et al. 2006

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“…Therefore, GR is critical for maintaining a high GSH:GSSG ratio and the cell's protection against oxidative stress. Inhibition of GR can decrease the ratio of GSH to GSSG and increase intracellular TRS (19). Therefore, a potent, readily obtainable, and selective GR inhibitor would be a valuable research tool in studying TRS-related normal or abnormal biochemical processes.…”

Section: Thiol Redox State (Trs)mentioning

confidence: 99%

Characterization of a Novel Dithiocarbamate Glutathione Reductase Inhibitor and Its Use as a Tool to Modulate Intracellular Glutathione

Seefeldt

Zhao

Chen

et al. 2009

Journal of Biological Chemistry

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Thiol redox state (TRS) is an important parameter to reflect intracellular oxidative stress and is associated with various normal and abnormal biochemical processes. Agents that can be used to increase intracellular TRS will be valuable tools in TRS-related research. Glutathione reductase (GR) is a critical enzyme in the homeostasis of TRS. The enzyme catalyzes the reduction of GSSG to GSH to maintain a high GSH:GSSG ratio. Inhibition of the enzyme can be used to increase TRS. Despite the reports of various GR inhibitors, N,N-bis(2-chloroethyl)-N-nitrosourea, an anticancer drug with IC 50 ‫؍‬ 647 M against yeast GR, remains the most commonly used GR inhibitor in the literature. However, the toxicity caused by nonspecific interactions, as well as inhibition of DNA synthesis, complicates the use of N,N-bis(2-chloroethyl)-N-nitrosourea as a GR inhibitor. We report 2-acetylamino-3-[4-(2-acetylamino-2-carboxyethylsulfanylthiocarbonylamino)phenylthiocarbamoylsulfanyl]propionic acid (2-AAPA) as a novel irreversible GR inhibitor. 2-AAPA was prepared by one-step synthesis from commercially available reagents. The K i and k inact of 2-AAPA against yeast GR were determined to be 56 M and 0.1 min ؊1 , respectively. At the concentration that produced >80% yeast GR inhibition, 2-AAPA showed no inhibition against glutamylcysteine synthetase, glutathione synthetase, catalase, and superoxide dismutase, but minimal inhibition against glutathione S-transferase and glutathione peroxidase. In CV-1 cells, 2-AAPA (0.1 mM) produced 97% GR inhibition, 25% GSH reduction, and a 5-fold increase in GSSG in 20 min. The compound can be a useful tool in TRS-related research.

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“…Each sample was split into two separate 500 ml aliquots, one for the determination of total non-protein-bound glutathione and glutathione disulfide (GSH þ GSSG) and the second for the determination of oxidized GSSG. 15,16 For the determination of GSSG, the samples were supplemented with N-ethylmaleimide (3.8 mM) to alkylate-free thiol groups. Proteins were precipitated with 100 ml cold 18% perchloric acid.…”

Section: Phenotypic Analysismentioning

confidence: 99%