scholarly journals Prenatal indole-3-carbinol administration activates aryl hydrocarbon receptor-responsive genes and attenuates lung injury in a bronchopulmonary dysplasia model 

2020 ◽  
pp. 153537022096378
Author(s):  
Gabriela Guzmán-Navarro ◽  
Mario Bermúdez de León ◽  
Irene Martín-Estal ◽  
Raquel Cuevas-Díaz Durán ◽  
Laura Villarreal-Alvarado ◽  
...  
Keyword(s):  
Lung Injury ◽  
Aryl Hydrocarbon Receptor ◽  
Signaling Pathway ◽  
Bronchopulmonary Dysplasia ◽  
Quantitative Polymerase Chain Reaction ◽  
Control Group ◽  
Hypoxia Exposure ◽  
Unexposed Control ◽  
Aryl Hydrocarbon ◽  
Rat Pups

Hyperoxia−hypoxia exposure is a proposed cause of alveolar developmental arrest in bronchopulmonary dysplasia in preterm infants, where mitochondrial reactive oxygen species and oxidative stress vulnerability are increased. The aryl hydrocarbon receptor (AhR) is one of the main activators of the antioxidant enzyme system that protects tissues and systems from damage. The present study aimed to determine if the activation of the AhR signaling pathway by prenatal administration of indole-3-carbinol (I3C) protects rat pups from hyperoxia–hypoxia-induced lung injury. To assess the activation of protein-encoding genes related to the AhR signaling pathway ( Cyp1a1, Cyp1b1, Ugt1a6, Nqo1, and Gsta1), pup lungs were excised at 0, 24, and 72 h after birth, and mRNA expression levels were quantified by reverse transcription-quantitative polymerase chain reaction assays (RT-qPCR). An adapted Ratner's method was used in rats to evaluate radial alveolar counts (RACs) and the degree of fibrosis. The results reveal that the relative expression of AhR-related genes in rat pups of prenatally I3C-treated dams was significantly different from that of untreated dams. The RAC was significantly lower in the hyperoxia–hypoxia group (4.0 ± 1.0) than that in the unexposed control group (8.0 ± 2.0; P <  0.01). When rat pups of prenatally I3C-treated dams were exposed to hyperoxia–hypoxia, an RAC recovery was observed, and the fibrosis index was similar to that of the unexposed control group. A cytokine antibody array revealed an increase in the NF-κB signaling cascade in I3C-treated pups, suggesting that the pathway could regulate the inflammatory process under the stimulus of this compound. In conclusion, the present study demonstrates that I3C prenatal treatment activates AhR-responsive genes in pup’s lungs and hence attenuates lung damage caused by hyperoxia–hypoxia exposure in newborns.

scholarly journals A comprehensive contribution of genes for aryl hydrocarbon receptor signaling pathway to hypertension susceptibility

2017 ◽  
Vol 27 (2) ◽  
pp. 57-69 ◽  
Author(s):  
Alexey V. Polonikov ◽  
Olga Yu. Bushueva ◽  
Irina V. Bulgakova ◽  
Maxim B. Freidin ◽  
Mikhail I. Churnosov ◽  
...  
Keyword(s):  
Aryl Hydrocarbon Receptor ◽  
Signaling Pathway ◽  
Receptor Signaling ◽  
Aryl Hydrocarbon ◽  
Receptor Signaling Pathway

scholarly journals Study and Determination of Aryl Hydrocarbon Receptor with Some Trace Elements in Fuel Filling Station Workers

2020 ◽  
Vol 10 (4) ◽  
pp. 233-251
Author(s):  
Bassem Abd Al-Raheem Twaij ◽  
Dr. Muthana Salam Mashkour ◽  
Dr.Hussein Kadhem Al-Hakeim
Keyword(s):  
Trace Elements ◽  
Serum Concentration ◽  
Aryl Hydrocarbon Receptor ◽  
Negative Correlation ◽  
Aromatic Hydrocarbons ◽  
Significant Negative Correlation ◽  
Correlation Study ◽  
Control Group ◽  
Aryl Hydrocarbon ◽  
Filling Station

PollutiOn is the intrOduction Of contaminantsʹ intO the natural envirOnment that cause adverseʹ change. Gasoline is a toxic and highly flammable liquid consists of various types of aliphatic hydrocarbons, olefins, benzenes and aromatic hydrocarbons including toluene, xylene and a large number of volatile compounds in addition to tetraethyl lead. Gasoline consists of different types of aliphatic hydrocarbons, aryl compounds and some trace elements. Trace elements are several important roles in human bodies, some are essential for enzymes reactions where they attract and facilitate conversion of substrate molecules to specific end products. Aryl hydrocarbon receptor (AHR) is a receptor involved in the regulation of biological responses to planar aromatic hydrocarbons.       The aim of the present study is to compare the serum AHR level in the fuel station workers (FSW) with the non-workers as a control group. The other aim is to find out a possible correlation between AHR with trace elements.              Sixty male FSW and 30 controls, from ten fuel stations at Al-Najaf City-Iraq, were participated in the present study. The AHR level in serum was measured using ELISA technique. Determine the following metal ions Zn2+, Cu2+, Fe3+, Mg2+, Na+ and K+ level in filling station workers (FSW) and control group were measured spectrophotometrically by using ready for use kits. Serum Pb level was carried out using Atomic absorption spectroscopy.              The results serum concentration of AHR in FSW group revealed a significant increase (p<0.001) as compared with the control group. No significant difference was noticed in AHR as compered in exposure ≥12years with exposure <12years in FWS. Smoking has no significant correlation with other parameters. Correlation study indicated a correlation between AHR and Age. Serum concentration of Cu2+, Zn2+, K+ and Pb in FSW group revealed a significant increase (p<0.001) as compared with the control group. While Fe3+, Na+ and Mg2+ in FSW group revealed a significant decrease (p<0.001) as compared with the control group. Correlation study indicated a significant negative correlation between serum Pb and AHR while other trace elements showed no significant correlation with AHR in FSW group. There is a significant negative correlation between serum Cu2+ with age while there is significant increase correlation between Zn2+, Mg2+ and Pb with age in FWS group.                 Conclusion of study is The role of increase AHR on the health in FSW group, attention to use safety gloves and face mask is recommended for FSW and a long follow-up to the studied group is necessary to explore the    prognosis of increase AHR in FSW.  

scholarly journals Hepatic Transcriptome Reveals That Fructose Downregulated Xenobiotics Metabolizing Enzymes Through Aryl Hydrocarbon Receptor Signaling Suppression in C57BL/6 N Mice (P15-011-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Jeong Hoon Pan ◽  
Jingsi Tang ◽  
Kaleigh Beane ◽  
Mersady Redding ◽  
Jiangchao Zhao ◽  
...  
Keyword(s):  
Aryl Hydrocarbon Receptor ◽  
Signaling Pathway ◽  
Bioinformatic Analysis ◽  
University Of Arkansas ◽  
Rt Pcr ◽  
Aryl Hydrocarbon ◽  
Fructose Intake ◽  
Upstream Regulator ◽  
Mice Liver ◽  
The University

Abstract Objectives For decades, fructose intake has been recognized as an environmental risk for metabolic syndromes and diseases. Thus, we comprehensively examined the effects of fructose intake on mice liver transcriptomes. Methods Fructose supplemented water (34%; wt/vol) was fed to both male and female C57BL/6 N mice at their free will for six weeks, followed by hepatic transcriptomics analysis. Based on our criteria, differentially expressed genes (DEGs) were selected and subjected to further computational analyses to predict key pathways and upstream regulator(s). Subsequently, predicted genes and pathways from the transcriptomics dataset were validated via quantitative RT-PCR analyses. Results As results, we identified 89 down-regulated and 88 up-regulated mRNAs in fructose-fed mice livers. These DEGs were subjected to bioinformatic analysis tools in which DEGs were mainly enriched in xenobiotic metabolic processes; further, in the Ingenuity Pathway Analysis software, it was suggested that the aryl hydrocarbon receptor (AhR) is an upstream regulator governing overall changes while fructose suppresses the AhR signaling pathway. In our quantitative RT-PCR validation, we confirmed that fructose suppressed AhR signaling through modulating expressions of transcription factor (arnt) and upstream regulators (ncor2, and rb1). Conclusions Altogether, we demonstrated that ad libitum fructose intake suppresses the canonical AhR signaling pathway in C57BL/6 N mice liver. Based on our current observations, further studies are warranted, especially with regard to the effects of co-exposure to fructose on 1) other types of carcinogens and 2) inflammation inducing agents (or even diets such as a high-fat diet), to find implications of fructose induced-AhR suppression. Funding Sources This work was supported by the University of Arkansas, VPRED Start-up fund and Dale Bumpers College of Agricultural, Food and Life Sciences. Support has been also provided in part by the Arkansas Biosciences Institute, a partnership of scientists from Arkansas Children's Hospital, Arkansas State University, the University of Arkansas-Division of Agriculture, the University of Arkansas, Fayetteville, and the University of Arkansas for Medical Sciences. The Arkansas Biosciences Institute is the major research component of the Arkansas Tobacco Settlement Proceeds Act of 2000. Supporting Tables, Images and/or Graphs

scholarly journals Inhibition of PTEN Gene Expression by Small Interfering RNA on PI3K/Akt/FoxO3a Signaling Pathway in Human Nasopharyngeal Carcinoma

2020 ◽  
Vol 19 ◽  
pp. 153303382091795
Author(s):  
Liang Zhong Yao ◽  
Yan Li Zhu ◽  
Jun Jie Liu
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Signaling Pathway ◽  
Messenger Rna ◽  
Small Interfering Rna ◽  
Quantitative Polymerase Chain Reaction ◽  
Pten Gene ◽  
Control Group ◽  
Expression Levels ◽  
Human Nasopharyngeal Carcinoma ◽  
Interfering Rna

The objective of this article is to study the effect of inhibiting phosphatase and tensin homolog deleted chromatosome 10 gene on phosphoinositide 3-kinase/protein kinase B ( Akt)/Forkhead homeobox O3a signaling pathway in human nasopharyngeal carcinoma HK-1 cells. Nasopharyngeal carcinoma HK-1 cell lines were divided into PTEN gene interference group (siPTEN), nonspecific small interfering RNA group (siNC), empty vector group (Vector), and no transfection control group (Normal). The mRNA and protein expression levels of PTEN, PI3K, p-Akt, and FoxO3a were detected by real-time fluorescence quantitative polymerase chain reaction and Western blot. Immunofluorescence was used to detect the subcellular localization of PTEN, PI3K, p-Akt, and FoxO3a in HK-1 cells. The proliferation of HK-1 cells was detected by MTT assay, and the apoptosis of HK-1 cells was detected by flow cytometry. Compared with the siNC group, the expression levels of PTEN, FoxO3a messenger RNA, and protein in the siPTEN group were significantly decreased ( P < .05), while the expression levels of PI3K, p-Akt messenger RNA, and protein were significantly increased ( P < .05). The growth rate of HK-1 cells in the siPTEN group was significantly higher than the siNC group ( P < .05), while the apoptosis rate was significantly lower than that of the siNC group ( P < .05). Small interfering RNA can inhibit the expression of PTEN in HK-1 cells, and PTEN can participate in the development of NPC by affecting PI3K/Akt/FoxO3a signaling pathway.

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