Full Text Journal Articles by
Author Bruce A Freeman

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Olanzapine-induced liver injury in mice: aggravation by high-fat diet and protection with sulforaphane.

Robin H Isaacson, Juliane I Beier, Nicholas Kh Khoo, Bruce A Freeman, Zachary Freyberg, Gavin E Arteel,

Olanzapine is effective to treat for schizophrenia and other mood disorders, but limited by side effects such as weight gain, dyslipidemia, and liver injury. Obesity in the US is at epidemic levels, and is a significant risk factor for drug-induced liver injury. Obesity incidence in the psychiatric population is even ... Read more >>

J. Nutr. Biochem. (The Journal of nutritional biochemistry)
[2020, 81:108399]

Cited: 0 times

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Novel gene regulatory networks identified in response to nitro-conjugated linoleic acid in human endothelial cells.

Haocheng Lu, Jinjian Sun, Wenying Liang, Jifeng Zhang, Oren Rom, Minerva T Garcia-Barrio, Shengdi Li, Luis Villacorta, Francisco J Schopfer, Bruce A Freeman, Y Eugene Chen, Yanbo Fan,

Endothelial cell (EC) dysfunction is a crucial initiation event in the development of atherosclerosis and is associated with diabetes mellitus, hypertension, and heart failure. Both digestive and oxidative inflammatory conditions lead to the endogenous formation of nitrated derivatives of unsaturated fatty acids (FAs) upon generation of the proximal nitrating species ... Read more >>

Physiol. Genomics (Physiological genomics)
[2019, 51(6):224-233]

Cited: 0 times

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Redox properties and human serum albumin binding of nitro-oleic acid.

Martina Zatloukalova, Milos Mojovic, Aleksandra Pavicevic, Martin Kabelac, Bruce A Freeman, Michaela Pekarova, Jan Vacek,

Nitro-fatty acids modulate inflammatory and metabolic stress responses, thus displaying potential as new drug candidates. Herein, we evaluate the redox behavior of nitro-oleic acid (NO2-OA) and its ability to bind to the fatty acid transporter human serum albumin (HSA). The nitro group of NO2-OA underwent electrochemical reduction at -0.75 V at pH ... Read more >>

Redox Biol (Redox Biology)
[2019, 24:101213]

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Electrophilic nitro-oleic acid reverses obesity-induced hepatic steatosis.

Nicholas K H Khoo, Marco Fazzari, Dionysios V Chartoumpekis, Lihua Li, Danielle Aparecida Guimaraes, Gavin E Arteel, Sruti Shiva, Bruce A Freeman,

Non-alcoholic fatty liver disease (NAFLD) is linked to obesity and insulin resistance and is the most prevalent chronic liver disease. During the development of obesity and NAFLD, mitochondria adapt to the increased lipid load in hepatocytes by increasing the rate of fatty acid oxidation. In concert with this, reactive species ... Read more >>

Redox Biol (Redox Biology)
[2019, 22:101132]

Cited: 1 time

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Electrophilic fatty acids impair RAD51 function and potentiate the effects of DNA-damaging agents on growth of triple-negative breast cells.

Alparslan Asan, John J Skoko, Chen-Shan Chen Woodcock, Bentley M Wingert, Steven R Woodcock, Daniel Normolle, Yi Huang, Jeremy M Stark, Carlos J Camacho, Bruce A Freeman, Carola A Neumann,

Homologous recombination (HR)-directed DNA double-strand break (DSB) repair enables template-directed DNA repair to maintain genomic stability. RAD51 recombinase (RAD51) is a critical component of HR and facilitates DNA strand exchange in DSB repair. We report here that treating triple-negative breast cancer (TNBC) cells with the fatty acid nitroalkene 10-nitro-octadec-9-enoic acid ... Read more >>

J. Biol. Chem. (The Journal of biological chemistry)
[2019, 294(2):397-404]

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Electrophiles modulate glutathione reductase activity via alkylation and upregulation of glutathione biosynthesis.

Soma Jobbagy, Dario A Vitturi, Sonia R Salvatore, Lucía Turell, Maria F Pires, Emilia Kansanen, Carlos Batthyany, Jack R Lancaster, Bruce A Freeman, Francisco J Schopfer,

Cells evolved robust homeostatic mechanisms to protect against oxidation or alkylation by electrophilic species. Glutathione (GSH) is the most abundant intracellular thiol, protects cellular components from oxidation and is maintained in a reduced state by glutathione reductase (GR). Nitro oleic acid (NO2-OA) is an electrophilic fatty acid formed under digestive ... Read more >>

Redox Biol (Redox Biology)
[2019, 21:101050]

Cited: 2 times

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Electrophilic nitroalkene-tocopherol derivatives: synthesis, physicochemical characterization and evaluation of anti-inflammatory signaling responses.

Jorge Rodriguez-Duarte, Rosina Dapueto, Germán Galliussi, Lucía Turell, Andrés Kamaid, Nicholas K H Khoo, Francisco J Schopfer, Bruce A Freeman, Carlos Escande, Carlos Batthyány, Gerardo Ferrer-Sueta, Gloria V López,

Inflammation plays a major role in the onset and development of chronic non-communicable diseases like obesity, cardiovascular diseases and cancer. Combined, these diseases represent the most common causes of death worldwide, thus development of novel pharmacological approaches is crucial. Electrophilic nitroalkenes derived from fatty acids are formed endogenously and exert ... Read more >>

Sci Rep (Scientific reports)
[2018, 8(1):12784]

Cited: 0 times

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Synthesis of an Electrophilic Keto-Tetraene 15-oxo-Lipoxin A4 Methyl Ester via a MIDA Boronate.

Steven R Woodcock, Stacy G Wendell, Francisco J Schopfer, Bruce A Freeman,

15-oxo-Lipoxin A4 (15-oxo- LXA4) has been identified as a natural metabolite of the fatty acid signaling mediator Lipoxin A4. Herein, we report a total synthesis of the methyl ester of 15-oxo-LXA4 to be used in investigations of potential electrophilic bioactivity of this metabolite. The methyl ester of 15-oxo-LXA4 was synthesized ... Read more >>

Tetrahedron Lett. (Tetrahedron letters)
[2018, 59(39):3524-3527]

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Nitro-fatty acids: New drug candidates for chronic inflammatory and fibrotic diseases.

Francisco J Schopfer, Dario A Vitturi, Diane K Jorkasky, Bruce A Freeman,

Nitrated oleic acid (NO2-OA) was first identified in 2003, and after the characterization of its formation and thiol reactivity, it was used as a prototypical molecule to investigate the physiological actions of endogenous nitrated fatty acids (NO2-FA). Based on in vitro observations showing significant activation of cytoprotective and anti-inflammatory signaling ... Read more >>

Nitric Oxide (Nitric oxide : biology and chemistry)
[2018, 79:31-37]

Cited: 6 times

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The discovery of nitro-fatty acids as products of metabolic and inflammatory reactions and mediators of adaptive cell signaling.

Bruce A Freeman, Valerie B O'Donnell, Francisco J Schopfer,

Foundational advances in eicosanoid signaling, the free radical biology of oxygen and nitric oxide and mass spectrometry all converged to enable the discovery of nitrated unsaturated fatty acids. Due to the unique biochemical characteristics of fatty acid nitroalkenes, these species undergo rapid and reversible Michael addition of biological nucleophiles such ... Read more >>

Nitric Oxide (Nitric oxide : biology and chemistry)
[2018, 77:106-111]

Cited: 2 times

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Transcriptomic sequencing reveals diverse adaptive gene expression responses of human vascular smooth muscle cells to nitro-conjugated linoleic acid.

Shengdi Li, Ziyi Chang, Tianqing Zhu, Luis Villacorta, Yixue Li, Bruce A Freeman, Y Eugene Chen, Jifeng Zhang,

Nitro-conjugated linoleic acid (NO2-CLA) is formed by metabolic and inflammatory reactions of nitric oxide and nitrite, and represents the most abundant nitro-fatty acid species in humans. These electrophilic fatty acid nitroalkene derivatives mediate pleiotropic cell signaling responses. Here, we report a systematic approach to investigate the effect of NO2-CLA on ... Read more >>

Physiol. Genomics (Physiological genomics)
[2018, 50(4):287-295]

Cited: 1 time

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Topical electrophilic nitro-fatty acids potentiate cutaneous inflammation.

Alicia R Mathers, Cara D Carey, Meaghan E Killeen, Sonia R Salvatore, Laura K Ferris, Bruce A Freeman, Francisco J Schopfer, Louis D Falo,

Endogenous electrophilic fatty acids mediate anti-inflammatory responses by modulating metabolic and inflammatory signal transduction and gene expression. Nitro-fatty acids and other electrophilic fatty acids may thus be useful for the prevention and treatment of immune-mediated diseases, including inflammatory skin disorders. In this regard, subcutaneous (SC) injections of nitro oleic acid ... Read more >>

Free Radic. Biol. Med. (Free radical biology & medicine)
[2018, 115:31-42]

Cited: 1 time

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Conjugated Linoleic Acid Modulates Clinical Responses to Oral Nitrite and Nitrate.

Kara S Hughan, Stacy Gelhaus Wendell, Meghan Delmastro-Greenwood, Nicole Helbling, Catherine Corey, Landon Bellavia, Gopal Potti, George Grimes, Bret Goodpaster, Daniel B Kim-Shapiro, Sruti Shiva, Bruce A Freeman, Mark T Gladwin,

Dietary NO3- (nitrate) and NO2- (nitrite) support ˙NO (nitric oxide) generation and downstream vascular signaling responses. These nitrogen oxides also generate secondary nitrosating and nitrating species that react with low molecular weight thiols, heme centers, proteins, and unsaturated fatty acids. To explore the kinetics of NO3-and NO2-metabolism and the impact ... Read more >>

Hypertension (Hypertension (Dallas, Tex. : 1979))
[2017, 70(3):634-644]

Cited: 5 times

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Nitro-oleic acid regulates growth factor-induced differentiation of bone marrow-derived macrophages.

Hana Verescakova, Gabriela Ambrozova, Lukas Kubala, Tomas Perecko, Adolf Koudelka, Ondrej Vasicek, Tanja K Rudolph, Anna Klinke, Steven R Woodcock, Bruce A Freeman, Michaela Pekarova,

Many diseases accompanied by chronic inflammation are connected with dysregulated activation of macrophage subpopulations. Recently, we reported that nitro-fatty acids (NO2-FAs), products of metabolic and inflammatory reactions of nitric oxide and nitrite, modulate macrophage and other immune cell functions. Bone marrow cell suspensions were isolated from mice and supplemented with ... Read more >>

Free Radic. Biol. Med. (Free radical biology & medicine)
[2017, 104:10-19]

Cited: 2 times

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Nitro-Oleic Acid Prevents Hypoxia- and Asymmetric Dimethylarginine-Induced Pulmonary Endothelial Dysfunction.

Adolf Koudelka, Gabriela Ambrozova, Anna Klinke, Tana Fidlerova, Hana Martiskova, Radek Kuchta, Tanja K Rudolph, Jaroslav Kadlec, Zdenka Kuchtova, Steven R Woodcock, Bruce A Freeman, Lukas Kubala, Michaela Pekarova,

Pulmonary hypertension (PH) represents a serious health complication accompanied with hypoxic conditions, elevated levels of asymmetric dimethylarginine (ADMA), and overall dysfunction of pulmonary vascular endothelium. Since the prevention strategies for treatment of PH remain largely unknown, our study aimed to explore the effect of nitro-oleic acid (OA-NO2), an exemplary nitro-fatty ... Read more >>

Cardiovasc Drugs Ther (Cardiovascular drugs and therapy)
[2016, 30(6):579-586]

Cited: 3 times

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Enterosalivary nitrate metabolism and the microbiome: Intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health.

Carl D Koch, Mark T Gladwin, Bruce A Freeman, Jon O Lundberg, Eddie Weitzberg, Alison Morris,

Recent insights into the bioactivation and signaling actions of inorganic, dietary nitrate and nitrite now suggest a critical role for the microbiome in the development of cardiac and pulmonary vascular diseases. Once thought to be the inert, end-products of endothelial-derived nitric oxide (NO) heme-oxidation, nitrate and nitrite are now considered ... Read more >>

Free Radic. Biol. Med. (Free radical biology & medicine)
[2017, 105:48-67]

Cited: 18 times

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Nitro-oleic acid inhibits vascular endothelial inflammatory responses and the endothelial-mesenchymal transition.

Gabriela Ambrozova, Tana Fidlerova, Hana Verescakova, Adolf Koudelka, Tanja K Rudolph, Steven R Woodcock, Bruce A Freeman, Lukas Kubala, Michaela Pekarova,

Inflammatory-mediated pathological processes in the endothelium arise as a consequence of the dysregulation of vascular homeostasis. Of particular importance are mediators produced by stimulated monocytes/macrophages inducing activation of endothelial cells (ECs). This is manifested by excessive soluble pro-inflammatory mediator production and cell surface adhesion molecule expression. Nitro-fatty acids are endogenous ... Read more >>

Biochim. Biophys. Acta (Biochimica et biophysica acta)
[2016, 1860(11 Pt A):2428-2437]

Cited: 7 times

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Novel Roles for Peroxynitrite in Angiotensin II and CaMKII Signaling.

Chaoming Zhou, Swarna S Ramaswamy, Derrick E Johnson, Dario A Vitturi, Franciso J Schopfer, Bruce A Freeman, Andy Hudmon, Edwin S Levitan,

Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) oxidation controls excitability and viability. While hydrogen peroxide (H2O2) affects Ca(2+)-activated CaMKII in vitro, Angiotensin II (Ang II)-induced CaMKIIδ signaling in cardiomyocytes is Ca(2+) independent and requires NADPH oxidase-derived superoxide, but not its dismutation product H2O2. To better define the biological regulation of CaMKII activation ... Read more >>

Sci Rep (Scientific reports)
[2016, 6:23416]

Cited: 1 time

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Electrophilic nitro-fatty acids prevent astrocyte-mediated toxicity to motor neurons in a cell model of familial amyotrophic lateral sclerosis via nuclear factor erythroid 2-related factor activation.

Pablo Diaz-Amarilla, Ernesto Miquel, Andrés Trostchansky, Emiliano Trias, Ana M Ferreira, Bruce A Freeman, Patricia Cassina, Luis Barbeito, Marcelo R Vargas, Homero Rubbo,

Nitro-fatty acids (NO2-FA) are electrophilic signaling mediators formed in tissues during inflammation, which are able to induce pleiotropic cytoprotective and antioxidant pathways including up regulation of Nuclear factor erythroid 2-related factor 2 (Nrf2) responsive genes. Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease characterized by the loss of motor ... Read more >>

Free Radic. Biol. Med. (Free radical biology & medicine)
[2016, 95:112-120]

Cited: 5 times

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Nitro-fatty acids in cardiovascular regulation and diseases: characteristics and molecular mechanisms.

Luis Villacorta, Zhen Gao, Francisco J Schopfer, Bruce A Freeman, Y Eugene Chen,

Electrophilic nitro-fatty acids (NO2-FAs) are endogenously formed by redox reactions of nitric oxide ((.)NO)- and nitrite ((.)NO2)- derived nitrogen dioxide with unsaturated fatty acids. Nitration preferentially occurs on polyunsaturated fatty acids with conjugated dienes under physiological or pathophysiological conditions such as during digestion, metabolism and as adaptive inflammatory processes. Nitro-fatty ... Read more >>

Front Biosci (Landmark Ed) (Frontiers in bioscience (Landmark edition))
[2016, 21:873-889]

Cited: 10 times

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Nitro-oleic acid modulates classical and regulatory activation of macrophages and their involvement in pro-fibrotic responses.

Gabriela Ambrozova, Hana Martiskova, Adolf Koudelka, Thorben Ravekes, Tanja K Rudolph, Anna Klinke, Volker Rudolph, Bruce A Freeman, Steven R Woodcock, Lukas Kubala, Michaela Pekarova,

Inflammation is an immune response triggered by microbial invasion and/or tissue injury. While acute inflammation is directed toward invading pathogens and injured cells, thus enabling tissue regeneration, chronic inflammation can lead to severe pathologies and tissue dysfunction. These processes are linked with macrophage polarization into specific inflammatory "M1-like" or regulatory ... Read more >>

Free Radic. Biol. Med. (Free radical biology & medicine)
[2016, 90:252-260]

Cited: 19 times

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Nitrated fatty acids suppress angiotensin II-mediated fibrotic remodelling and atrial fibrillation.

Tanja K Rudolph, Thorben Ravekes, Anna Klinke, Kai Friedrichs, Martin Mollenhauer, Michaela Pekarova, Gabriela Ambrozova, Hana Martiskova, Jatinder-Jit Kaur, Bianca Matthes, Alex Schwoerer, Steven R Woodcock, Lukas Kubala, Bruce A Freeman, Stephan Baldus, Volker Rudolph,

Atrial fibrosis, one of the most striking features in the pathology of atrial fibrillation (AF), is promoted by local and systemic inflammation. Electrophilic fatty acid nitroalkenes, endogenously generated by both metabolic and inflammatory reactions, are anti-inflammatory mediators that in synthetic form may be useful as drug candidates. Herein we investigate ... Read more >>

Cardiovasc. Res. (Cardiovascular research)
[2016, 109(1):174-184]

Cited: 13 times

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Activation of TRPC channels contributes to OA-NO2-induced responses in guinea-pig dorsal root ganglion neurons.

Xiulin Zhang, Jonathan M Beckel, Stephanie L Daugherty, Ting Wang, Stephen R Woodcock, Bruce A Freeman, William C de Groat,

Effects of nitro-oleic acid (OA-NO2) on TRP channels were examined in guinea-pig dissociated dorsal root ganglia (DRG) neurons using calcium imaging and patch clamp techniques. OA-NO2 increased intracellular Ca(2+) in 60-80% DRG neurons. 1-Oleoyl-2acetyl-sn-glycerol (OAG), a TRPC agonist, elicited responses in 36% of OA-NO2-sensitive neurons while capsaicin (TRPV1 agonist) or ... Read more >>

J. Physiol. (Lond.) (The Journal of physiology)
[2014, 592(19):4297-4312]

Cited: 4 times

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Protective effects of 10-nitro-oleic acid in a hypoxia-induced murine model of pulmonary hypertension.

Anna Klinke, Annika Möller, Michaela Pekarova, Thorben Ravekes, Kai Friedrichs, Matthias Berlin, Katrin M Scheu, Lukas Kubala, Hana Kolarova, Gabriela Ambrozova, Ralph T Schermuly, Steven R Woodcock, Bruce A Freeman, Stephan Rosenkranz, Stephan Baldus, Volker Rudolph, Tanja K Rudolph,

Pulmonary arterial hypertension (PAH) is characterized by adverse remodeling of pulmonary arteries. Although the origin of the disease and its underlying pathophysiology remain incompletely understood, inflammation has been identified as a central mediator of disease progression. Oxidative inflammatory conditions support the formation of electrophilic fatty acid nitroalkene derivatives, which exert ... Read more >>

Am. J. Respir. Cell Mol. Biol. (American journal of respiratory cell and molecular biology)
[2014, 51(1):155-162]

Cited: 21 times

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Protection from hypertension in mice by the Mediterranean diet is mediated by nitro fatty acid inhibition of soluble epoxide hydrolase.

Rebecca L Charles, Olena Rudyk, Oleksandra Prysyazhna, Alisa Kamynina, Jun Yang, Christophe Morisseau, Bruce D Hammock, Bruce A Freeman, Philip Eaton,

Soluble epoxide hydrolase (sEH) is inhibited by electrophilic lipids by their adduction to Cys521 proximal to its catalytic center. This inhibition prevents hydrolysis of the enzymes' epoxyeicosatrienoic acid (EET) substrates, so they accumulate inducing vasodilation to lower blood pressure (BP). We generated a Cys521Ser sEH redox-dead knockin (KI) mouse model ... Read more >>

Proc. Natl. Acad. Sci. U.S.A. (Proceedings of the National Academy of Sciences of the United States of America)
[2014, 111(22):8167-8172]

Cited: 38 times

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