scholarly journals Environmental pollutants-dependent molecular pathways and carcinogenesis

Biodiscovery ◽  
2019 ◽  
Vol 22 ◽  
Author(s):  
Myriam El Helou ◽  
Pascale A. Cohen ◽  
Mona Diab-Assaf ◽  
Sandra Ghayad
Keyword(s):  
Gene Expression ◽  
Environmental Pollutants ◽  
Environmental Chemicals ◽  
Gene Repair ◽  
Hormone Production ◽  
Aryl Hydrocarbon ◽  
Repair Mechanisms ◽  
Cellular Signal ◽  
And Function ◽  
G Protein Coupled

Exposure to environmental pollutants can modulate many biological and molecular processes such as gene expression, gene repair mechanisms, hormone production and function and inflammation, resulting in adverse effects on human health including the occurrence and development of different types of cancer. Carcinogenesis is a complex and long process, taking place in multiple stages and is affected by multiple factors. Some environmental molecules are genotoxic, able to damage the DNA or to induce mutations and changes in gene expression acting as initiators of carcinogenesis. Other molecules called xenoestrogens can promote carcinogenesis by their mitogenic effects by possessing estrogenic-like activities and consequently acting as endocrine disruptors causing multiple alterations in cellular signal transduction pathways. In this review, we focus on recent research on environmental chemicals-driven molecular functions in human cancers. For this purpose, we will be discussing the case of two receptors in mediating environmental pollutants effects: the established nuclear receptor, the Aryl hydrocarbon receptor (AhR) and the emerging membrane receptor, G-protein coupled estrogen receptor 1 (GPER1).

scholarly journals Metatranscriptomic Analysis of the Mouse Gut Microbiome Response to the Persistent Organic Pollutant 2,3,7,8-Tetrachlorodibenzofuran

Metabolites ◽  
2019 ◽  
Vol 10 (1) ◽  
pp. 1
Author(s):  
Robert G. Nichols ◽  
Jingtao Zhang ◽  
Jingwei Cai ◽  
Iain A. Murray ◽  
Imhoi Koo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gut Microbiome ◽  
Structural Changes ◽  
Organic Pollutant ◽  
Amplicon Sequencing ◽  
Environmental Chemicals ◽  
Rrna Gene ◽  
Aryl Hydrocarbon ◽  
Biosynthesis Gene ◽  
And Function

Persistent organic pollutants (POPs) are important environmental chemicals and continued study of their mechanism of action remains a high priority. POPs, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 2,3,7,8-tetrachlorodibenzofuran (TCDF), and polychlorinated biphenyls (PCBs), are widespread environmental contaminants that are agonists for the aryl hydrocarbon receptor (AHR). Activation of the AHR modulates the gut microbiome community structure and function, host immunity, and the host metabolome. In the current study, male C57BL6/J mice were exposed, via the diet, to 5 µg/kg body weight (BW) TCDF or 24 µg/kg BW of TCDF every day for 5 days. The functional and structural changes imparted by TCDF exposure to the gut microbiome and host metabolome were explored via 16S rRNA gene amplicon sequencing, metabolomics, and bacterial metatranscriptomics. Significant changes included increases in lipopolysaccharide (LPS) biosynthesis gene expression after exposure to 24 µg/kg BW of TCDF. Increases in LPS biosynthesis were confirmed with metabolomics and LPS assays using serum obtained from TCDF-treated mice. Significant increases in gene expression within aspartate and glutamate metabolism were noted after exposure to 24 µg/kg BW of TCDF. Together, these results suggest that after exposure to 24 µg/kg BW of TCDF, the gut microbiome increases the production of LPS and glutamate to promote localized gut inflammation, potentially using glutamate as a stress response.

scholarly journals G-Protein Coupled Receptors (GPCRs): Signaling Pathways, Characterization, and Functions in Insect Physiology and Toxicology

2021 ◽  
Vol 22 (10) ◽  
pp. 5260
Author(s):  
Nannan Liu ◽  
Yifan Wang ◽  
Ting Li ◽  
Xuechun Feng
Keyword(s):  
Gene Expression ◽  
Insecticide Resistance ◽  
Signaling Pathways ◽  
G Protein ◽  
G Protein Coupled Receptors ◽  
Cell Physiology ◽  
Insect Physiology ◽  
Wide Range ◽  
And Function ◽  
G Protein Coupled

G-protein-coupled receptors (GPCRs) are known to play central roles in the physiology of many organisms. Members of this seven α-helical transmembrane protein family transduce the extracellular signals and regulate intracellular second messengers through coupling to heterotrimeric G-proteins, adenylate cyclase, cAMPs, and protein kinases. As a result of the critical function of GPCRs in cell physiology and biochemistry, they not only play important roles in cell biology and the medicines used to treat a wide range of human diseases but also in insects’ physiological functions. Recent studies have revealed the expression and function of GPCRs in insecticide resistance, improving our understanding of the molecular complexes governing the development of insecticide resistance. This article focuses on the review of G-protein coupled receptor (GPCR) signaling pathways in insect physiology, including insects’ reproduction, growth and development, stress responses, feeding, behaviors, and other physiological processes. Hormones and polypeptides that are involved in insect GPCR regulatory pathways are reviewed. The review also gives a brief introduction of GPCR pathways in organisms in general. At the end of the review, it provides the recent studies on the function of GPCRs in the development of insecticide resistance, focusing in particular on our current knowledge of the expression and function of GPCRs and their downstream regulation pathways and their roles in insecticide resistance and the regulation of resistance P450 gene expression. The latest insights into the exciting technological advances and new techniques for gene expression and functional characterization of the GPCRs in insects are provided.

scholarly journals Aryl Hydrocarbon Receptor Repressor Is Hypomethylated in Psoriasis and Promotes Psoriasis-like Inflammation in HaCaT Cells

2021 ◽  
Vol 22 (23) ◽  
pp. 12715
Author(s):  
Ji-Young Um ◽  
Bo-Young Chung ◽  
Han-Bi Kim ◽  
Jin-Cheol Kim ◽  
Chun-Wook Park ◽  
...  
Keyword(s):  
Gene Expression ◽  
Aryl Hydrocarbon Receptor ◽  
Inflammatory Cytokines ◽  
Skin Diseases ◽  
Environmental Pollutants ◽  
Luciferase Reporter ◽  
Hacat Cells ◽  
Dna Hypomethylation ◽  
Aryl Hydrocarbon ◽  
Specific Pcr

It is known that DNA hypomethylation of aryl hydrocarbon receptor repressor (AhRR), one of the epigenetic markers of environmental pollutants, causes skin diseases. However, the function and mechanisms are still unknown. We aimed to determine whether AhRR is hypomethylated in PBMC of psoriasis patients, as well as to examine the expression of psoriasis-related inflammatory cytokines and antimicrobial peptides after 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) treatment in HaCaT cells overexpressing or silencing AhRR. AhRR was determined by qPCR, Western blot, immunohistochemistry, and immunocytochemistry in skin tissue and HaCaT cells. DNA methylation of AhRR was performed by Infinium Human Methylation450 BeadChip in PBMC of psoriasis patients and methylation-specific PCR (MSP) in HaCaT cells. NF-κB pp50 translocation and activity were performed by immunocytochemistry and luciferase reporter assay, respectively. We verified AhRR gene expression in the epidermis from psoriasis patients and healthy controls. AhRR hypomethylation in PBMC of psoriasis patients and pAhRR-HaCaT cells was confirmed. The expression level of AhRR was increased in both TCDD-treated HaCaT cells and pAhRR-HaCaT cells. NF-κB pp50 translocation and activity increased with TCDD. Our results showed that AhRR was hypomethylated and overexpressed in the lesional skin of patients with psoriasis, thereby increasing AhRR gene expression and regulating pro-inflammatory cytokines through the NF-κB signaling pathway in TCDD-treated HaCaT cells.

scholarly journals Mediating Roles of PPARs in the Effects of Environmental Chemicals on Sex Steroids

PPAR Research ◽  
2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Qiansheng Huang ◽  
Qionghua Chen
Keyword(s):  
Reproductive System ◽  
Sex Steroids ◽  
Environmental Pollutants ◽  
Environmental Chemicals ◽  
Peroxisome Proliferator ◽  
Altered Expression ◽  
In Silico Docking ◽  
Peroxisome Proliferator Activated Receptors ◽  
Peroxisome Proliferator Response Element ◽  
And Function

Peroxisome proliferator-activated receptors (PPARs) are ligand-activated nuclear receptors that are widely involved in various physiological functions. They are widely expressed through the reproductive system. Their roles in the metabolism and function of sex steroids and thus the etiology of reproductive disorders receive great concern. Various kinds of exogenous chemicals, especially environmental pollutants, exert their adverse impact on the reproductive system through disturbing the PPAR signaling pathway. Chemicals could bind to PPARs and modulate the transcription of downstream genes containing PPRE (peroxisome proliferator response element). This will lead to altered expression of genes related to metabolism of sex steroids and thus the abnormal physiological function of sex steroids. In this review, various kinds of environmental ligands are summarized and discussed. Their interactions with three types of PPARs are classified by various data from transcript profiles, PPRE reporter in cell line, in silico docking, and gene silencing. The review will contribute to the understanding of the roles of PPARs in the reproductive toxicology of environmental chemicals.

scholarly journals The Role of Aryl-Hydrocarbon Receptor (AhR) in Osteoclast Differentiation and Function

Cells ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 2294
Author(s):  
Robin Park ◽  
Shreya Madhavaram ◽  
Jong Dae Ji
Keyword(s):  
Aryl Hydrocarbon Receptor ◽  
Osteoclast Differentiation ◽  
Environmental Pollutants ◽  
Endogenous Ligand ◽  
Aryl Hydrocarbon ◽  
Binding Time ◽  
Functional Regulation ◽  
Exogenous Ligands ◽  
And Function

Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that plays a crucial role in bone remodeling through altering the interplay between bone-forming osteoblasts and bone-resorbing osteoclasts. While effects of AhR signaling in osteoblasts are well understood, the role and mechanism of AhR signaling in regulating osteoclastogenesis is not widely understood. AhR, when binding with exogenous ligands (environmental pollutants such as polycylic aryl hydrocarbon (PAH), dioxins) or endogenous ligand indoxyl-sulfate (IS), has dual functions that are mediated by the nature of the binding ligand, binding time, and specific pathways of distinct ligands. In this review, AhR is discussed with a focus on (i) the role of AhR in osteoclast differentiation and function and (ii) the mechanisms of AhR signaling in inhibiting or promoting osteoclastogenesis. These findings facilitate an understanding of the role of AhR in the functional regulation of osteoclasts and in osteoclast-induced bone destructive conditions such as rheumatoid arthritis and cancer.

scholarly journals Gpr1 is an active chemerin receptor influencing glucose homeostasis in obese mice

2014 ◽  
Vol 222 (2) ◽  
pp. 201-215 ◽  
Author(s):  
Jillian L Rourke ◽  
Shanmugam Muruganandan ◽  
Helen J Dranse ◽  
Nichole M McMullen ◽  
Christopher J Sinal
Keyword(s):  
Adipose Tissue ◽  
Glucose Homeostasis ◽  
Stromal Vascular Fraction ◽  
Tolerance Test ◽  
Glucose Levels ◽  
Brown Adipose ◽  
Elevated Glucose ◽  
And Function ◽  
G Protein Coupled

Chemerin is an adipose-derived signaling protein (adipokine) that regulates adipocyte differentiation and function, immune function, metabolism, and glucose homeostasis through activation of chemokine-like receptor 1 (CMKLR1). A second chemerin receptor, G protein-coupled receptor 1 (GPR1) in mammals, binds chemerin with an affinity similar to CMKLR1; however, the function of GPR1 in mammals is essentially unknown. Herein, we report that expression of murineGpr1mRNA is high in brown adipose tissue and white adipose tissue (WAT) and skeletal muscle. In contrast to chemerin (Rarres2) andCmklr1,Gpr1expression predominates in the non-adipocyte stromal vascular fraction of WAT. Heterozygous and homozygousGpr1-knockout mice fed on a high-fat diet developed more severe glucose intolerance than WT mice despite having no difference in body weight, adiposity, or energy expenditure. Moreover, mice lackingGpr1exhibited reduced glucose-stimulated insulin levels and elevated glucose levels in a pyruvate tolerance test. This study is the first, to our knowledge, to report the effects ofGpr1deficiency on adiposity, energy balance, and glucose homeostasisin vivo. Moreover, these novel results demonstrate that GPR1 is an active chemerin receptor that contributes to the regulation of glucose homeostasis during obesity.

scholarly journals Roles of HIF and 2-Oxoglutarate-Dependent Dioxygenases in Controlling Gene Expression in Hypoxia

Cancers ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 350
Author(s):  
Julianty Frost ◽  
Mark Frost ◽  
Michael Batie ◽  
Hao Jiang ◽  
Sonia Rocha
Keyword(s):  
Gene Expression ◽  
Hypoxia Inducible Factor ◽  
Transcriptional Regulator ◽  
Hydroxylase Activity ◽  
Control Of Gene Expression ◽  
Prolyl Hydroxylases ◽  
Chromatin Organisation ◽  
Sense And Respond ◽  
Almost All ◽  
And Function

Hypoxia—reduction in oxygen availability—plays key roles in both physiological and pathological processes. Given the importance of oxygen for cell and organism viability, mechanisms to sense and respond to hypoxia are in place. A variety of enzymes utilise molecular oxygen, but of particular importance to oxygen sensing are the 2-oxoglutarate (2-OG) dependent dioxygenases (2-OGDs). Of these, Prolyl-hydroxylases have long been recognised to control the levels and function of Hypoxia Inducible Factor (HIF), a master transcriptional regulator in hypoxia, via their hydroxylase activity. However, recent studies are revealing that dioxygenases are involved in almost all aspects of gene regulation, including chromatin organisation, transcription and translation. We highlight the relevance of HIF and 2-OGDs in the control of gene expression in response to hypoxia and their relevance to human biology and health.

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