Digital Commons Network^™

Microglial P2y12 Receptor Regulates Ventral Hippocampal Ca1 Neuronal Excitability And Innate Fear In Mice, Jiyun Peng, Yong Liu, Anthony D. Umpierre, Manling Xie, Dai-Shi Tian, Jason Richardson, Long-Jun Wu

Environmental Health Sciences

The P2Y12 receptor (P2Y12R) is a purinoceptor that is selectively expressed in microglia in the central nervous system. As a signature receptor, microglial P2Y12R mediates process chemotaxis towards ADP/ATP gradients and is engaged in several neurological diseases including chronic pain, stroke and seizures. However, the role of microglial P2Y12R in regulating neuronal excitability and innate behaviors is not fully understood. Here, we generated P2Y12-floxed mice to delete microglial P2Y12R beginning in development (CX3CR1Cre/+:P2Y12f/f; “constitutive knockout”), or after normal development in adult mice (CX3CR1CreER/+:P2Y12f/f; “induced knockout”). Using a battery of behavioral tests, we found that both constitutive and induced P2Y12R knockout …

Effect Of Transcriptional Regulator Id3 On Pulmonary Arterial Hypertension And Hereditary Hemorrhagic Telangiectasia, Vincent Avecilla

Environmental Health Sciences

Pulmonary arterial hypertension (PAH) can be discovered in patients who have a loss of function mutation of activin A receptor-like type 1 (ACVRL1) gene, a bone morphogenetic protein (BMP) type 1 receptor. Additionally, ACVRL1 mutations can lead to hereditary hemorrhagic telangiectasia (HHT), also known as Rendu-Osler-Weber disease, an autosomal dominant inherited disease that results in mucocutaneous telangiectasia and arteriovenous malformations (AVMs). Transcriptional regulator Inhibitor of DNA-Binding/Differentiation-3 (ID3) has been demonstrated to be involved in both PAH and HTT; however, the role of its overlapping molecular mechanistic effects has yet to be seen. This review …

Microglia Are Indispensable For Synaptic Plasticity In The Spinal Dorsal Horn And Chronic Pain, Li-Jun Zhou, Jiyun Peng, Ya-Nan Xu, Jun Zhang, Xiao Wei, Chun-Lin Mai, Yong Liu, Madhuvika Murugan, Ukpong B. Eyo, Anthony D. Umpierre, Wen-Jun Xin, Tao Chen, Mingtao Li, Hui Wang, Jason Richardson, Zhi Tan, Xian-Guo Liu, Long-Jun Wu

Environmental Health Sciences

Spinal long-term potentiation (LTP) at C-fiber synapses is hypothesized to underlie chronic pain. However, a causal link between spinal LTP and chronic pain is still lacking. Here, we report that high-frequency stimulation (HFS; 100 Hz, 10 V) of the mouse sciatic nerve reliably induces spinal LTP without causing nerve injury. LTP-inducible stimulation triggers chronic pain lasting for more than 35 days and increases the number of calcitonin gene-related peptide (CGRP) terminals in the spinal dorsal horn. The behavioral and morphological changes can be prevented by blocking NMDA receptors, ablating spinal microglia, or conditionally deleting microglial brain-derived neurotrophic factor (BDNF). HFS-induced …

Phosphoregulation On Mitochondria: Integration Of Cell And Organelle Responses, Maribel Lucero, Ana E. Suarez, Jeremy W. Chambers

Environmental Health Sciences

Mitochondria are highly integrated organelles that are crucial to cell adaptation and mitigating adverse physiology. Recent studies demonstrate that fundamental signal transduction pathways incorporate mitochondrial substrates into their biological programs. Reversible phosphorylation is emerging as a useful mechanism to modulate mitochondrial function in accordance with cellular changes. Critical serine/threonine protein kinases, such as the c‐Jun N‐terminal kinase (JNK), protein kinase A (PKA), PTEN‐induced kinase‐1 (PINK1), and AMP‐dependent protein kinase (AMPK), readily translocate to the outer mitochondrial membrane (OMM), the interface of mitochondria‐cell communication. OMM protein kinases phosphorylate diverse mitochondrial substrates that have discrete effects on organelle dynamics, protein import, respiratory …

Vitamin E Inhibits The Uvai Induction Of “Light” And “Dark” Cyclobutane Pyrimidine Dimers, And Oxidatively Generated Dna Damage, In Keratinocytes, George J. Delinasios, Mahsa Karbaschi, Marcus Cooke, Antony R. Young

Environmental Health Sciences

Solar ultraviolet radiation (UVR)-induced DNA damage has acute, and long-term adverse effects in the skin. This damage arises directly by absorption of UVR, and indirectly via photosensitization reactions. The aim of the present study was to assess the effects of vitamin E on UVAI-induced DNA damage in keratinocytes in vitro. Incubation with vitamin E before UVAI exposure decreased the formation of oxidized purines (with a decrease in intracellular oxidizing species), and cyclobutane pyrimidine dimers (CPD). A possible sunscreening effect was excluded when similar results were obtained following vitamin E addition after UVAI exposure. Our data showed that DNA damage …

Inhibitor Of Differentiation-3 And Estrogenic Endocrine Disruptors: Implications For Susceptibility To Obesity And Metabolic Disorders, Mayur Doke, Vincent Avecilla, Quentin Felty

Environmental Health Sciences

The rising global incidence of obesity cannot be fully explained within the context of traditional risk factors such as an unhealthy diet, physical inactivity, aging, or genetics. Adipose tissue is an endocrine as well as a metabolic organ that may be susceptible to disruption by environmental estrogenic chemicals. Since some of the endocrine disruptors are lipophilic chemicals with long half-lives, they tend to bioaccumulate in the adipose tissue of exposed populations. Elevated exposure to these chemicals may predispose susceptible individuals to weight gain by increasing the number and size of fat cells. Genetic studies have demonstrated that the transcriptional regulator …

Mitochondria: A Common Target For Genetic Mutations And Environmental Toxicants In Parkinson’S Disease, Martin P. Helley, Jennifer Pinnell, Carolina Sportelli, Kim Tieu

Environmental Health Sciences

Parkinson’s disease (PD) is a devastating neurological movement disorder. Since its first discovery 200 years ago, genetic and environmental factors have been identified to play a role in PD development and progression. Although genetic studies have been the predominant driving force in PD research over the last few decades, currently only a small fraction of PD cases can be directly linked to monogenic mutations. The remaining cases have been attributed to other risk associated genes, environmental exposures and gene–environment interactions, making PD a multifactorial disorder with a complex etiology. However, enormous efforts from global research have yielded significant insights into …

Mitochondrial Division Inhibitor-1 Is Neuroprotective In The A53t-Α-Synuclein Rat Model Of Parkinson’S Disease, Simone Bido, Federico N. Soria, Rebecca Z. Fan, Erwan Bezard, Kim Tieu

Environmental Health Sciences

Alpha-synuclein (α-syn) is involved in both familial and sporadic Parkinson’s disease (PD). One of the proposed pathogenic mechanisms of α-syn mutations is mitochondrial dysfunction. However, it is not entirely clear the impact of impaired mitochondrial dynamics induced by α-syn on neurodegeneration and whether targeting this pathway has therapeutic potential. In this study we evaluated whether inhibition of mitochondrial fission is neuroprotective against α-syn overexpression in vivo. To accomplish this goal, we overexpressed human A53T-α- synuclein (hA53T-α-syn) in the rat nigrostriatal pathway, with or without treatment using the small molecule Mitochondrial Division Inhibitor-1 (mdivi-1), a putative inhibitor of the mitochondrial …

Contribution Of Inhibitor Of Dna Binding/Differentiation-3 And Endocrine Disrupting Chemicals To Pathophysiological Aspects Of Chronic Disease, Vincent Avecilla, Mayur Doke, Quentin Felty

Environmental Health Sciences

The overwhelming increase in the global incidence of obesity and its associated complications such as insulin resistance, atherosclerosis, pulmonary disease, and degenerative disorders including dementia constitutes a serious public health problem. The Inhibitor of DNA Binding/Differentiation-3 (ID3), a member of the ID family of transcriptional regulators, has been shown to play a role in adipogenesis and therefore ID3 may influence obesity andmetabolic health in response to environmental factors.This reviewwill highlight the current understanding of howID3may contribute to complex chronic diseases viametabolic perturbations. Based on the increasing number of reports that suggest chronic exposure to and accumulation of endocrine disrupting chemicals …

Gender, Estrogen, And Obliterative Lesions In The Lung, Hamza Assaggaf, Quentin Felty

Environmental Health Sciences

Gender has been shown to impact the prevalence of several lung diseases such as cancer, asthma, chronic obstructive pulmonary disease, and pulmonary arterial hypertension (PAH). Controversy over the protective effects of estrogen on the cardiopulmonary system should be of no surprise as clinical trials of hormone replacement therapy have failed to show benefits observed in experimental models. Potential confounders to explain these inconsistent estrogenic effects include the dose, cellular context, and systemic versus local tissue levels of estrogen. Idiopathic PAH is disproportionately found to be up to 4 times more common in females than in males; however, estrogen levels cannot …

Endogenously Generated Dna Nucleobase Modifications Source, And Significance As Possible Biomarkers Of Malignant Transformation Risk, And Role In Anticancer Therapy, Ryszard Olinski, Daniel Gackowskia, Marcus Cooke

Environmental Health Sciences

The DNA of all living cells undergoes continuous structural and chemical alteration, which may be derived from exogenous sources, or endogenous, metabolic pathways, such as cellular respiration, replication and DNA demethylation. It has been estimated that approximately 70,000 DNA lesions may be generated per day in a single cell, and this has been linked to a wide variety of diseases, including cancer. However, it is puzzling why potentially mutagenic DNA modifications, occurring at a similar level in different organs/tissue, may lead to organ/tissue specific cancers, or indeed non-malignant disease – what is the basis for this differential response? We suggest …

Imaging Of Glial Cell Activation And White Matter Integrity In Brains Of Active And Recently Retired National Football League Players, Jennifer Coughlin, Yuchuan Wang, Ii Minn, Nicholas Bienko, Emily B. Ambinder, Xin Xu, Matthew E. Peters, John W. Dougherty, Melin Vranesic, Soo Min Koo, Hye-Hyun Ahn, Merton Lee, Chris Cottrell, Haris I. Sair, Akira Sawa, Cynthia A. Munro, Christopher J. Nowinski, Robert F. Dannals, Constantine G. Lyketsos, Michael Kassiou, Gwenn Smith, Brian Caffo, Susumu Mori, Tomás R. Guilarte, Martin G. Pomper

Environmental Health Sciences

Importance:

Microglia, the resident immune cells of the central nervous system, play an important role in the brain's response to injury and neurodegenerative processes. It has been proposed that prolonged microglial activation occurs after single and repeated traumatic brain injury, possibly through sports-related concussive and subconcussive injuries. Limited in vivo brain imaging studies months to years after individuals experience a single moderate to severe traumatic brain injury suggest widespread persistent microglial activation, but there has been little study of persistent glial cell activity in brains of athletes with sports-related traumatic brain injury.

Objective:

To measure translocator protein 18 kDa (TSPO), …

Estrogenic Endocrine Disrupting Chemicals Influencing Nrf1 Regulated Gene Networks In The Development Of Complex Human Brain Diseases, Mark Preciados, Changwon Yoo, Deodutta Roy

Environmental Health Sciences

During the development of an individual from a single cell to prenatal stages to adolescence to adulthood and through the complete life span, humans are exposed to countless environmental and stochastic factors, including estrogenic endocrine disrupting chemicals. Brain cells and neural circuits are likely to be influenced by estrogenic endocrine disruptors (EEDs) because they strongly dependent on estrogens. In this review, we discuss both environmental, epidemiological, and experimental evidence on brain health with exposure to oral contraceptives, hormonal therapy, and EEDs such as bisphenol-A (BPA), polychlorinated biphenyls (PCBs), phthalates, and metalloestrogens, such as, arsenic, cadmium, and manganese. Also we discuss …

Association Between Exposure To Estrogenic Endocrine Disruptors - Polychlorinated Biphenyls, Phthalates, And Bisphenol A And Gynecologic Cancers- Cervical, Ovarian, Uterine Cancers, Marisa Morgan, Alok Deoraj, Quentin Felty, Changwon Yoo, Deodutta Roy

Environmental Health Sciences

No abstract provided.

Differences In The Carcinogenic Evaluation Of Glyphosate Between The International Agency For Research On Cancer (Iarc) And The European Food Safety Authority (Efsa), Christopher J. Portier, Bruce K. Armstrong, Bruce C. Baguley, Deodutta Roy

Environmental Health Sciences

The International Agency for Research on Cancer (IARC) Monographs Programme identifies chemicals, drugs, mixtures, occupational exposures, lifestyles and personal habits, and physical and biological agents that cause cancer in humans and has evaluated about 1000 agents since 1971. Monographs are written by ad hoc Working Groups (WGs) of international scientific experts over a period of about 12 months ending in an eight-day meeting. The WG evaluates all of the publicly available scientific information on each substance and, through a transparent and rigorous process,1 decides on the degree to which the scientific evidence supports that substance's potential to cause or …

Urinary 8-Oxo-7,8-Dihydro-2'-Deoxyguanosine Analysis By An Improved Elisa: Does Assay Standardization Reduce Inter-Laboratory Variability?, Pavel Rossner Jr., Hilmi Orhan, Regina M. Santella, Kazuo Sakai, Gudrun Koppen, Antonin Ambroz, Andrea Rossnerova, Radim J. Sram, Miroslav Ciganek, Jiri Neca, Marcus Cooke

Environmental Health Sciences

ELISA is commonly used for the detection of urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), a marker of whole body oxidative stress. However, the method has been criticized for high inter-laboratory variability and poor agreement with chromatographic techniques. We performed an inter-laboratory comparison of 8-oxodG assessed in 30 urine samples and a urine spiked with four different concentrations of 8-oxodG by ELISA using standardized experimental conditions, including: sample pre-treatment with solid-phase extraction (SPE), performing analysis using a commercial kit from a single manufacturer and strict temperature control during the assay. We further compared the ELISA results with high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) and …

Nucleotide Excision Repair Of Oxidised Genomic Dna Is Not A Source Of Urinary 8-Oxo-7,8-Dihydro-2’-Deoxyguanosine, Mark D. Evans, Vilas Misty, Rajinder Singh, Daniel Gackowski, Rafał Różalski, Agnieszka Siomek-Gorecka, David H. Phillips, Jie Zuo, Leon Mullenders, Alex Pines, Yusaku Nakabeppu, Kunihiko Sakumi, Mutsuo Sekiguchi, Teruhisa Tsuzuki, Margherita Bignami, Ryszard Oliński, Marcus Cooke

Environmental Health Sciences

Urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) is a widely measured biomarker of oxidative stress. It has been commonly assumed to be a product of DNA repair, and therefore reflective of DNA oxidation. However, the source of urinary 8-oxodGuo is not understood, although potential confounding contributions from cell turnover and diet have been ruled out. Clearly it is critical to understand the precise biological origins of this important biomarker, so that the target molecule that is oxidised can be identified, and the significance of its excretion can be interpreted fully. In the present study we aimed to assess the contributions of nucleotide excision repair …

Microvascular Lesions By Estrogen-Induced Id3: Its Implications In Cerebral & Cardiorenal Vascular Disease, Jayanta K. Das, Quentin Felty

Environmental Health Sciences

Severe symptoms of cerebral and cardiorenal vascular diseases can be triggered when cerebral, coronary, or glomerular arterioles grow inappropriately as a result of abnormal cell proliferation. The risk factor(s) and molecular mechanisms responsible for microvascular lesion formation are largely unknown. Although controversial, both animal and epidemiological studies have shown that estrogen increases the risk of stroke which may be due to microvascular lesions. Since microvascular diseases are characterized by excessive vessel growth, it is plausible that estrogen-induced neovascularization contributes to the growth of microvascular lesions. We present evidence for how ID3 overexpression in endothelial cells contributes to the development of …

Vascular Endothelial Growth Factor Receptor 3 Signaling Contributes To Angioobliterative Pulmonary Hypertension, Ayser Al-Husseini, Donatas Kraskauskas, Eleanora Mezzaroma, Andrea Nordio, Daniela Farkas, Jennifer I. Drake, Antonio Abbate, Quentin Felty, Norbert F. Voelkel

Environmental Health Sciences

The mechanisms involved in the development of severe angioobliterative pulmonary arterial hypertension (PAH) are multicellular and complex. Many of the features of human severe PAH, including angioobliteration, lung perivascular inflammation, and right heart failure, are reproduced in the Sugen 5416/chronic hypoxia (SuHx) rat model. Here we address, at first glance, the confusing and paradoxical aspect of the model, namely, that treatment of rats with the antiangiogenic vascular endothelial growth factor (VEGF) receptor 1 and 2 kinase inhibitor, Sugen 5416, when combined with chronic hypoxia, causes angioproliferative pulmonary vascular disease. We postulated that signaling through the unblocked VEGF receptor VEGFR3 (or …

Id3 Contributes To The Acquisition Of Molecular Stem Cell-Like Signature In Microvascular Endothelial Cells: Its Implication For Understanding Microvascular Diseases, Jayanta K. Das, Norbert F. Voelkel, Quentin Felty

Environmental Health Sciences

While significant progress has been made to advance our knowledge of microvascular lesion formation, yet the investigation of how stem-like cells may contribute to the pathogenesis of microvascular diseases is still in its infancy. We assessed whether the inhibitor of DNA binding and differentiation 3 (ID3) contributes to the acquisition of a molecular stem cell-like signature in microvascular endothelial cells. The effects of stable ID3 overexpression and SU5416 treatment — a chemical inducer of microvascular lesions, had on the stemness signature was determined by flow cytometry, immunoblot, and immunohistochemistry. Continuous ID3 expression produced a molecular stemness signature consisting of CD133 …

8-Oxo-7,8-Dihydroguanine And 8-Oxo-7,8-Dihydro-2'-Deoxyguanosine Concentrations In Various Human Body Fluids: Implications For Their Measurement And Interpretation, Chiung-Wen Hu, Marcus Cooke, Yi-Hung Tsai, Mu-Rong Chao

Environmental Health Sciences

8-Oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) is the most investigated product of oxidatively damaged DNA lesion that has been associated with the development of aging, cancer and some degenerative diseases. Here, we present the first liquid chromatography-tandem mass spectrometry method that enables the simultaneous measurement of its repair products in plasma and saliva, namely 8-oxo-7,8-dihydroguanine (8-oxoGua) and 8-oxodGuo. Using this method, we investigated the underlying transport mechanism of the repair products of oxidatively damaged DNA between cellular compartments and biological matrices. Plasma, saliva and urine samples were collected concurrently from 57 healthy subjects. Various deproteinization methods were evaluated, and the precipitants acetonitrile and sodium …

Rescue Of Cells From Apoptosis Increases Dna Repair In Uvb Exposed Cells: Implications For The Dna Damage Response, Mahsa Karbaschi, Salvador Macip, Vilas Mistry, Hussein H.K. Abbas, George J. Delinassios, Mark D. Evans, Anthony R. Young, Marcus Cooke

Environmental Health Sciences

Classically, the nucleotide excision repair (NER) of cyclobutane pyrimidine dimers (CPD) is a lengthy process (t_1/2 > 48 h). Using the T4 endonuclease V-modified comet assay, we uniquely found a far more rapid repair of UVA-induced CPD (t_1/2 = 4.5 h) in human skin keratinocytes. The repair of UVB-induced CPD began to slow within 1 h of irradiation, causing damage to persist for over 36 h. A similar trend was noted for the repair of oxidatively-modified purine nucleobases. Supportive of this differential repair, we noted an up-regulation of key genes associated with NER in UVA-irradiated cells, whereas the same …

Increased Risk Of Childhood Brain Tumors Among Children Whose Parents Had Farm-Related Pesticide Exposures During Pregnancy, Brian Kunkle, S. Bae, K. P. Singh, Deodutta Roy

Environmental Health Sciences

Malignant brain tumors rank second in both incidence and mortality by cancer in children, and they are the leading cause of cancer death in children. Relatively little is known about the etiology of childhood brain tumor (CBT). While there are several studies which link pesticide exposure to increased risk of CBT, findings have been inconsistent. We performed a meta-analysis on 15 published epidemiological studies to test that in utero exposure to pesticides may be involved in the development of brain cancer in children. Meta-analysis was performed using the general variance-based method and homogeneity was tested by means of the Q …

Redox Signalling To Nuclear Regulatory Proteins By Reactive Oxygen Species Contributes To Oestrogen-Induced Growth Of Breast Cancer Cells, Victor Okoh, N. A. Garba, Jayanta K. Das, Alok Deoraj, K. P. Singh, S. Sarkar, Quentin Felty, Changwon Yoo, R. M. Jackson, Deodutta Roy

Environmental Health Sciences

Background:

17β-Oestradiol (E2)-induced reactive oxygen species (ROS) have been implicated in regulating the growth of breast cancer cells. However, the underlying mechanism of this is not clear. Here we show how ROS through a novel redox signalling pathway involving nuclear respiratory factor-1 (NRF-1) and p27 contribute to E2-induced growth of MCF-7 breast cancer cells.

Methods:

Chromatin immunoprecipitation, qPCR, mass spectrometry, redox western blot, colony formation, cell proliferation, ROS assay, and immunofluorescence microscopy were used to study the role of NRF-1.

Results:

The major novel finding of this study is the demonstration of oxidative modification of phosphatases PTEN and …

Pcb153-Induced Overexpression Of Id3 Contributes To The Development Of Microvascular Lesions, Jayanta K. Das, Quentin Felty

Environmental Health Sciences

Microvascular lesions resulting from endothelial cell dysfunction are produced in the brain, lung, kidney, and retina of patients of complex chronic diseases. The environmental and molecular risk factors which may contribute in the development of microvascular damage are unclear. The mechanism(s) responsible for initiating microvascular damage remain poorly defined, although several inciting factors have been proposed, including environmental toxicants-induced oxidative stress. Enhanced neovascularization has been implicated in either the development or progression of proliferative vascular lesions. Here, we present evidence for how PCB-induced ROS may contribute to the development of a neovascular phenotype with the aim of elucidating the role …

Reverse Engineering Of Modified Genes By Bayesian Network Analysis Defines Molecular Determinants Critical To The Development Of Glioblastoma, Brian W. Kunkle, Changwon Yoo, Deodutta Roy

Environmental Health Sciences

In this study we have identified key genes that are critical in development of astrocytic tumors. Meta-analysis of microarray studies which compared normal tissue to astrocytoma revealed a set of 646 differentially expressed genes in the majority of astrocytoma. Reverse engineering of these 646 genes using Bayesian network analysis produced a gene network for each grade of astrocytoma (Grade I–IV), and ‘key genes’ within each grade were identified. Genes found to be most influential to development of the highest grade of astrocytoma, Glioblastoma multiforme were: COL4A1, EGFR, BTF3, MPP2, RAB31, CDK4, CD99, ANXA2, TOP2A, and SERBP1. All of these genes …

Reactive Oxygen Species Via Redox Signaling To Pi3k/Akt Pathway Contribute To The Malignant Growth Of 4-Hydroxy Estradiol-Transformed Mammary Epithelial Cells, Victor Okoh, Quentin Felty, Jai Parkash, Robert Poppiti, Deodutta Roy

Environmental Health Sciences

The purpose of this study was to investigate the effects of 17-β-estradiol (E2)-induced reactive oxygen species (ROS) on the induction of mammary tumorigenesis. We found that ROS-induced by repeated exposures to 4-hydroxy-estradiol (4-OH-E2), a predominant catechol metabolite of E2, caused transformation of normal human mammary epithelial MCF-10A cells with malignant growth in nude mice. This was evident from inhibition of estrogen-induced breast tumor formation in the xenograft model by both overexpression of catalase as well as by co-treatment with Ebselen. To understand how 4-OH-E2 induces this malignant phenotype through ROS, we investigated the effects of 4-OH-E2 on redox-sensitive signal transduction …

Proteomic 2-D Dige Profiling Of Human Vascular Endothelial Cells Exposed To Environmentally Relevant Concentration Of Endocrine Disruptor Pcb153 And Physiological Concentration Of 17Β-Estradiol, Quentin Felty

Environmental Health Sciences

Considering the recent studies that question previously reported cardio-protective effects of estrogen, there is a growing concern that endocrine disruptors may also contribute to the pathology of cardiovascular disease (CVD). The endocrine disruptor PCB153 has been reported to bind the estrogen receptor, induce vessel formation, and increase the formation of reactive oxygen species (ROS) in endothelial cells. Since PCB153 induced phenotypic changes are similar to estradiol, we postulated that PCB153 activates redox signaling pathways common to 17β-estradiol. Whether the effect of PCB153 on the proteome is comparable to 17β-estradiol is not known. Therefore we investigated the proteome of human microvascular …

Gene Expression Profile Of Endothelial Cells Exposed To Estrogenic Environmental Compounds: Implications To Pulmonary Vascular Lesions, Quentin Felty, Changwon Yoo, Amy Kennedy

Environmental Health Sciences

Aims

The cardiovascular system is an important target of estrogenic compounds. Considering the recent studies that question previously reported cardio-protective effects of estrogen, there is a growing concern that estrogenic environmental compounds may contribute to the pathology of vascular lesion formation.

Main methods

Real-time quantitative PCR was used to monitor the expression of genes involved in vascularization. Using Bayesian network modeling, we determined a gene network that estrogenic chemicals modulate in human vascular endothelial cells.

Key findings

We showed that planar and co-planar polychlorinated biphenyls (PCBs) induce the expression of different genes compared to estradiol. Non-planar PCB congener 153 induced …

Proteomic 2d Dige Profiling Of Human Vascular Endothelial Cells Exposed To Environmentally Relevant Concentration Of Endocrine Disruptor Pcb153 And Physiological Concentration Of 17Β-Estradiol, Quentin Felty

Environmental Health Sciences

Considering the recent studies that question previously reported cardio-protective effects of estrogen, there is a growing concern that endocrine disruptors may also contribute to the pathology of cardiovascular disease. PCB153 is one of the most commonly found polychlorinated biphenyls, and based on epidemiological studies, has been implicated in cardiovascular disease. The endocrine disruptor PCB153 has been reported to bind the estrogen receptor alpha, induce vessel formation, and increase the formation of reactive oxygen species in endothelial cells. Since PCB153-induced phenotypic changes are similar to estradiol, we postulated that PCB153 activates redox signaling pathways common to 17β-estradiol. Whether the effect of …