A5072089972- Genomics, phytochemicals, and oxidative stress
- Glutathione Transferases and Polymorphisms
- Carcinogens and Genotoxicity Assessment
- Mycotoxins in Agriculture and Food
- Estrogen and related hormone effects
- Free Radicals and Antioxidants
- Liver Disease Diagnosis and Treatment
- Vitamin D Research Studies
- Synthesis and biological activity
- Sulfur Compounds in Biology
- Bioactive Compounds and Antitumor Agents
- Air Quality and Health Impacts
- Tea Polyphenols and Effects
- Synthesis and Biological Evaluation
- Garlic and Onion Studies
- Hepatitis B Virus Studies
- IL-33, ST2, and ILC Pathways
- DNA Repair Mechanisms
- Redox biology and oxidative stress
- Adipose Tissue and Metabolism
- Epigenetics and DNA Methylation
- Coenzyme Q10 studies and effects
- Biochemical and Molecular Research
- Health, Environment, Cognitive Aging
- Amino Acid Enzymes and Metabolism
Johns Hopkins University
2016-2025
Fred Hutch Cancer Center
2015-2025
University of Pittsburgh
2013-2024
Johns Hopkins Medicine
2008-2023
Center for Environmental Health
2023
University of Patras
2019
Harvard University
2019
University of Pittsburgh Medical Center
2019
UPMC Hillman Cancer Center
2011-2018
University of Memphis
2008-2018
Induction of phase 2 enzymes, which neutralize reactive electrophiles and act as indirect antioxidants, appears to be an effective means for achieving protection against a variety carcinogens in animals humans. Transcriptional control the expression these enzymes is mediated, at least part, through antioxidant response element (ARE) found regulatory regions their genes. The transcription factor Nrf2, binds ARE, essential induction prototypical such glutathione S -transferases (GSTs)...
Host genetic factors that regulate innate immunity determine susceptibility to sepsis. Disruption of nuclear factor-erythroid 2–related factor 2 (Nrf2), a basic leucine zipper transcription regulates redox balance and stress response, dramatically increased the mortality mice in response endotoxin- cecal ligation puncture–induced septic shock. LPS as well TNF-α stimulus resulted greater lung inflammation Nrf2-deficient mice. Temporal analysis pulmonary global gene expression after challenge...
Induction of a family phase 2 genes encoding for proteins that protect against the damage electrophiles and reactive oxygen intermediates is potentially major strategy reducing risk cancer chronic degenerative diseases. Many are regulated by upstream antioxidant response elements (ARE) targets leucine zipper transcription factor Nrf2. Under basal conditions, Nrf2 resides mainly in cytoplasm bound to its cysteine-rich, Kelch domain-containing partner Keap1, which itself anchored actin...
Although inflammation and protease/antiprotease imbalance have been postulated to be critical in cigarette smoke–induced (CS-induced) emphysema, oxidative stress has suspected play an important role chronic obstructive pulmonary diseases. Susceptibility of the lung injury, such as that originating from inhalation CS, depends largely on its upregulation antioxidant systems. Nuclear factor, erythroid-derived 2, like 2 (Nrf2) is a redox-sensitive basic leucine zipper protein transcription...
Although inflammation and protease/antiprotease imbalance have been postulated to be critical in cigarette smoke–induced (CS-induced) emphysema, oxidative stress has suspected play an important role chronic obstructive pulmonary diseases. Susceptibility of the lung injury, such as that originating from inhalation CS, depends largely on its upregulation antioxidant systems. Nuclear factor, erythroid-derived 2, like 2 (Nrf2) is a redox-sensitive basic leucine zipper protein transcription...
Gastric infection with Helicobacter pylori is a cosmopolitan problem, and especially common in developing regions where there also high prevalence of gastric cancer. These infections are known to cause gastritis peptic ulcers, dramatically enhance the risk Eradication this organism an important medical goal that complicated by development resistance conventional antimicrobial agents persistence low level reservoir H. within epithelial cells. Moreover, economic practical problems preclude...
Sulforaphane [1-isothiocyanato-4-(methyl-sulfinyl)butane] was recently isolated from one variety of broccoli as the major and very potent inducer phase 2 detoxication enzymes in murine hepatoma cells culture. Since enzyme induction is often associated with reduced susceptibility animals their to toxic neoplastic effects carcinogens other electrophiles, it important establish whether sulforaphane could block chemical carcinogenesis. In this paper we report that three synthetic analogues,...
The Nrf2 (nuclear factor E2 p45-related 2) transcription responds to diverse oxidative and electrophilic environmental stresses by circumventing repression Keap1, translocating the nucleus, activating cytoprotective genes. responses provide protection against chemical carcinogenesis, chronic inflammation, neurodegeneration, emphysema, asthma sepsis in murine models. regulates expression of a plethora genes that detoxify oxidants electrophiles repair or remove damaged macromolecules, such as...
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Enzyme inducers such as 3H-1,2-dithiole-3-thione (D3T) enhance the detoxication of environmental carcinogens and protect against neoplasia. The putative molecular sensor for is Keap1, a sulfhydryl-rich protein that sequesters transcription factor Nrf2 in cytoplasm. Expression these enzymes blunted nrf2-deficient mice; moreover, mice are more sensitive to carcinogenesis, protective actions dithiolethiones lost with nrf2 disruption. Hepatic gene expression profiles were examined by...
The dynamin-related guanosine triphosphatase Drp1 mediates the division of mitochondria and peroxisomes. To understand in vivo function Drp1, complete tissue-specific mouse knockouts were generated. Drp1-null mice die by embryonic day 11.5. This lethality is not likely caused gross energy deprivation, as cells showed normal intracellular adenosine triphosphate levels. In support role organelle division, formed extensive networks, peroxisomes elongated fibroblasts. Brain-specific ablation...
Induction of phase 2 enzymes, which neutralize reactive electrophiles and act as indirect antioxidants, is an important mechanism for protection against carcinogenesis. The transcription factor Nrf2, binds to the antioxidant response element (ARE) found in upstream regulatory region many genes, essential induction these enzymes. We have investigated effect potent enzyme inducer anticarcinogen 3H-1,2-dithiole-3-thione (D3T) on fate Nrf2 murine keratinocytes. Both total nuclear levels...
Oxidative stress has been postulated to play an important role in the pathogenesis of asthma; although a defect antioxidant responses speculated exacerbate asthma severity, this difficult demonstrate with certainty. Nuclear erythroid 2 p45-related factor (Nrf2) is redox-sensitive basic leucine zipper transcription that involved transcriptional regulation many genes. We show disruption Nrf2 gene leads severe allergen-driven airway inflammation and hyperresponsiveness mice. Enhanced asthmatic...
Rationale: Macrophages change their phenotype and biological functions depending on the microenvironment. In atherosclerosis, oxidative tissue damage accompanies chronic inflammation; however, macrophage phenotypic changes in response to oxidatively modified molecules are not known. Objective: To examine oxidized phospholipids that present atherosclerotic lesions. Methods Results: We show phospholipid-treated murine macrophages develop into a novel (Mox) is strikingly different from...
Proteasomes degrade damaged proteins formed during oxidative stress, thereby promoting cell survival.Neurodegenerative and other age-related disorders are associated with reduced proteasome activity.We show herein that expression of most subunits 20S 19S proteasomes, which collectively assemble the 26S proteasome, was enhanced up to threefold in livers mice following treatment dithiolethiones, act as indirect antioxidants.Subunit protein levels activity were coordinately increased.No...