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Barry L. Fanburg

Bio: Barry L. Fanburg is an academic researcher from Tufts Medical Center. The author has contributed to research in topics: Endothelial stem cell & Angiotensin-converting enzyme. The author has an hindex of 56, co-authored 221 publications receiving 13179 citations. Previous affiliations of Barry L. Fanburg include United States Department of Veterans Affairs & Brown University.


Papers
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Journal ArticleDOI
TL;DR: The evidence for ligand-induced generation of ROS, its cellular sources, and the signaling pathways that are activated is examined.
Abstract: Reactive oxygen species (ROS) are generated as by-products of cellular metabolism, primarily in the mitochondria. When cellular production of ROS overwhelms its antioxidant capacity, damage to cellular macromolecules such as lipids, protein, and DNA may ensue. Such a state of “oxidative stress” is thought to contribute to the pathogenesis of a number of human diseases including those of the lung. Recent studies have also implicated ROS that are generated by specialized plasma membrane oxidases in normal physiological signaling by growth factors and cytokines. In this review, we examine the evidence for ligand-induced generation of ROS, its cellular sources, and the signaling pathways that are activated. Emerging concepts on the mechanisms of signal transduction by ROS that involve alterations in cellular redox state and oxidative modifications of proteins are also discussed.

2,757 citations

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TL;DR: High levels of cellular GSH levels in cultured cells in response to hyperoxia or electrophilic agents such as diethylmaleate is coupled with an increase in activity of the Xc- transport system for the amino acids cystine and glutamate.
Abstract: In addition to its participation in a variety of other biochemical reactions, glutathione (GSH) is a major antioxidant. It is regularly generated intracellularly from its oxidized form by glutathione reductase activity that is coupled with a series of interrelated reactions. Synthesis of GSH also takes place intracellularly by a two-step reaction, the first of which is catalyzed by rate-limiting gamma-glutamylcysteine synthetase activity. Intracellular substrates for GSH are provided both by direct amino acid transport and by a gamma-glutamyl transpeptidase reaction that salvages circulating GSH by coupling the gamma-glutamyl moiety to a suitable amino acid acceptor for transport into the cell. Although the liver is a net synthesizer of circulating GSH, organs such as the kidney salvage GSH through the gamma-glutamyl transpeptidase reaction. Intracellular GSH may be consumed by GSH transferase reactions that conjugate GSH with certain xenobiotics. Elevation of cellular GSH levels in cultured cells in response to hyperoxia or electrophilic agents such as diethylmaleate is coupled with an increase in activity of the Xc- transport system for the amino acids cystine and glutamate. Strategies may be developed for protection against oxidant injury by enhancement of transport systems for precursor amino acids of GSH or by providing substrate that circumvents feedback inhibition of GSH synthesis.

850 citations

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TL;DR: It is shown that members of the STAT family of transcription factors are activated in fibroblasts and A-431 carcinoma cells in response to H2O2, indicating that the JAK-STAT pathway responds to intracellular ROS and that PDGF uses ROS as a second messenger to regulate STAT activation.
Abstract: Reactive oxygen species (ROS) play an important role in the pathogenesis of many human diseases, including the acute respiratory distress syndrome, Parkinson’s disease, pulmonary fibrosis, and Alzh...

544 citations

Journal ArticleDOI
TL;DR: Inhibitors of other enzymatic systems involving flavoproteins that may be responsible for the production of H2O2 in these cells, including xanthine oxidase, nitric oxide synthase, and both mitochondrial and microsomal electron transport systems, failed to inhibit TGF-β1-induced NADH oxidation and H2 O2 production.

432 citations

Journal ArticleDOI
TL;DR: The age range of women afflicted with pulmonary lymphangioleiomyomatosis is broader than previously appreciated and the degree of pulmonary function can be quite variable, with one-third of subjects having normal spirometry at enrollment into this registry.
Abstract: Rationale: Pulmonary lymphangioleiomyomatosis is a progressive cystic lung disease that is associated with infiltration of atypical smooth muscle–like cells. Previous descriptions of clinical characteristics of subjects with lymphangioleiomyomatosis have been based on a limited number of patients.Objectives: To describe the clinical characteristics of subjects with pulmonary lymphangioleiomyomatosis, both sporadic and tuberous sclerosis–related forms.Methods: Over a 3-yr period, from 1998 to 2001, 243 subjects with pulmonary lymphangioleiomyomatosis were enrolled into a national registry; 13 subjects who had already undergone lung transplantation were excluded for the purposes of this report.Measurements and Main Results: All 230 subjects were women, aged 18 to 76 yr (mean ± SE, 44.5 ± 0.65 yr). The average age at onset of symptoms was 38.9 ± 0.73 yr and at diagnosis was 41.0 ± 0.65 yr. Tuberous sclerosis complex was present in 14.8% of subjects. Pulmonary manifestations, most commonly spontaneous pneumot...

365 citations


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Journal ArticleDOI
TL;DR: Attention is focussed on the ROS/RNS-linked pathogenesis of cancer, cardiovascular disease, atherosclerosis, hypertension, ischemia/reperfusion injury, diabetes mellitus, neurodegenerative diseases, rheumatoid arthritis, and ageing.

12,240 citations

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TL;DR: There is growing evidence that aging involves, in addition, progressive changes in free radical-mediated regulatory processes that result in altered gene expression.
Abstract: At high concentrations, free radicals and radical-derived, nonradical reactive species are hazardous for living organisms and damage all major cellular constituents. At moderate concentrations, how...

9,131 citations

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TL;DR: This review examines the evidence for involvement of the oxidative stress in the carcinogenesis process and the role of enzymatic and non-enzymatic antioxidants in the process of carcinogenesis as well as the antioxidant interactions with various regulatory factors.

5,937 citations

Journal ArticleDOI
TL;DR: This review summarizes the current state of knowledge of the functions of NOX enzymes in physiology and pathology.
Abstract: For a long time, superoxide generation by an NADPH oxidase was considered as an oddity only found in professional phagocytes. Over the last years, six homologs of the cytochrome subunit of the phag...

5,873 citations

Journal ArticleDOI
TL;DR: Observations to date suggest that oxidative stress, chronic inflammation, and cancer are closely linked.

3,922 citations