Identification of common key regulators in rat hepatocyte cell lines under exposure of different pesticides

Sohrabi, Seyed Sajad; Rashidipour, Marzieh; Mohammadi, Mohsen; Fard, Javad Khalili; Najafgholi, Hossein Mirzaei

doi:10.1016/j.gene.2020.144508

Cited by 9 publications

(8 citation statements)

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“…Transcriptome changes was reported in zebrafish under conditions of deltamethrin or cypermethrin or niclosamide exposure. [ 47‐49 ] Differential gene expression in rat hepatocytes exposed to pesticides, [ 50 ] m 6 A methylome analyses in the testes of Xenopus laevis [ 51 ] were reported recently. In this study, the transcriptomic profile of genes associated with male germ cell production (spermatogenesis, steroidogenesis, and epigenetic modifications) was analyzed.…”

Section: Discussionmentioning

confidence: 99%

Effect of long‐term treatment with a mixture of pyrethroids on the expression of genes that govern male germ cell production in rats

Ravula

Yenugu

2020

J Biochem & Molecular Tox

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Humans are exposed to pyrethroid‐based pesticides through agricultural produce. In this study, male Wistar rats were orally treated for 9 to 12 months with a mixture of pyrethroids that is equivalent to one‐fifth (high dose; HD) or one‐twenty fifth (low dose; LD) of the amount of pyrethroids present in the cereals and rice consumed by an average Indian. In rats treated for 9 months, the spermatogenesis‐associated genes Abp, Ar, Cd9, Dax1, Dazap1, Ddx3y, Gdnf, Gfra1, Grth, Inhb, Ovol1, P1, Plzf, Pygo2, Scf, Tgfb1, Tp1, Tp2, and Vim1 were downregulated in both LD and HD groups. In rats treated for 12 months Gdnf, Hsf2, Inhb, Tgfb1, Thy1, and Ybx2 expression was downregulated in both LD and HD groups. Steroidogenesis‐associated genes 17‐β‐Hsd, Gata4, Hmgcr, Hmgcs1, Pde4b, and Tspo gene expression were reduced in both LD‐ and HD‐treated groups treated for 9 months. In 12‐month‐treated rats, Creb1 expression decreased in both LD and HD groups. The epigenetic reprogramming‐associated genes, Dnmt1, Dnmt3a, Dnmt3b, Hdac10, Hp1bp3, Kat3a Kat3b, Mch2ta, Ncoa7, and Sirt1 were downregulated in both HD and LD groups of 9‐months‐treated rats. In rats treated for 12 months, Hdac10, Mch2ta, Ncoa7, and Sirt1 messenger RNA levels decreased in both the HD and LD groups. Thus, we demonstrate that long‐term exposure to a mixture of pyrethroids caused aberrations in the transcriptome of factors involved in sperm production and development.

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Section: Discussionmentioning

confidence: 99%

Effect of long‐term treatment with a mixture of pyrethroids on the expression of genes that govern male germ cell production in rats

Ravula

Yenugu

2020

J Biochem & Molecular Tox

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“…It is important to highlight that the results presented above link the activation of PPARs receptors in in vitro and in vivo models to the development of obesity and diabetes, due to the interaction, activation, and biological responses (accumulation of lipids, adipogenesis, alteration in carbohydrates metabolism, insulin resistance); mainly with organotin pesticides (TBT and TPT) [21, 34, 43-45, 59, 76], followed by organophosphates (chlorpyrifos and DDT/DDE) [6,9,31,32,37,46,50,61,86]; however, the remaining pesticides such as pyrethroids, carbamates, and others show similar trends in terms of effects on PPARs as initially found for organotin and organophosphates. Therefore, further studies are needed to expand and clarify the mechanism by which pesticides might activate PPARs receptors and cause the development of obesity and diabetes mellitus.…”

Section: Discussionmentioning

confidence: 99%

“…The changes induced by the activation of PPARs due to interaction with pesticides have been linked to the development of obesity and type 2 diabetes mellitus [34,35]. The analysis is mainly based on the findings of differentially expressed genes (DEGs) [36] and transcription factors (TFs) [37], which are the main group of proteins that have a response to the exposure of a chemical substance and specifically increase biological conditions; the result can be associated through networks that allow to identify central and key genes in many diseases [29]. Alteration of PPARγ expression in the presence of toxaphene, methoxychlor, permethrin, atrazine, DDT, paraquat, and chlorpyrifos was described in microarray (RNA) analysis in a rat hepatocyte model, revealing changes in lipid and carbohydrate metabolism [37].…”

Section: Activation Of Ppars Bymentioning

confidence: 99%

“…The analysis is mainly based on the findings of differentially expressed genes (DEGs) [36] and transcription factors (TFs) [37], which are the main group of proteins that have a response to the exposure of a chemical substance and specifically increase biological conditions; the result can be associated through networks that allow to identify central and key genes in many diseases [29]. Alteration of PPARγ expression in the presence of toxaphene, methoxychlor, permethrin, atrazine, DDT, paraquat, and chlorpyrifos was described in microarray (RNA) analysis in a rat hepatocyte model, revealing changes in lipid and carbohydrate metabolism [37]. In another analysis of transcriptomics of HepaRG cells and exposure to quizalofop-pethyl, networks of genes associated with metabolic pathways involved in fatty acid degradation were identified.…”

Section: Activation Of Ppars Bymentioning

confidence: 99%

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Effect of Pesticides on Peroxisome Proliferator-Activated Receptors (PPARs) and Their Association with Obesity and Diabetes

2023

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Obesity and diabetes mellitus are considered the most important diseases of the XXI century. Recently, many epidemiological studies have linked exposure to pesticides to the development of obesity and type 2 diabetes mellitus. The role of pesticides and their possible influence on the development of these diseases was investigated by examining the relationship between these compounds and one of the major nuclear receptor families controlling lipid and carbohydrate metabolism: the peroxisome proliferator-activated receptors (PPARs), PPARα, PPARβ/δ, and PPARγ; this was possible through in silico, in vitro, and in vivo assays. The present review aims to show the effect of pesticides on PPARs and their contribution to the changes in energy metabolism that enable the development of obesity and type 2 diabetes mellitus.

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“…Myocyte enhancer factor 2A (MEF2A) inhibition abated activation of the TGF-β/SMAD signaling pathways [38]. The overexpression of speci city protein 1 (SP1) increased TGF-β1 expression levels and activated the TGF-β1/SMAD2 signaling pathway, while the downregulation of SP1 inhibited osteoblast differentiation [39,40].…”

Section: Discussionmentioning

confidence: 99%

Effect of strontium on transcription factors identified by transcriptome analyses of bovine ruminal epithelial cells

Tan,

Wang,

Mei

et al. 2023

Preprint

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Background: Strontium (Sr) has similar physicochemical properties as calcium (Ca) and is often used to evaluate the absorption of this mineral. Because the major route of Ca absorption in the bovine occurs in the rumen, it is essential to understand whether Sr impacts the ruminal epithelial cells and to what extent. Results: In the present study, RNA sequencing and assembled transcriptome assembly were used to identify transcription factors (TFs), screening and bioinformatics analysis in bovine ruminal epithelial cells treated with Sr. A total of 1405 TFs were identified and classified into 64 families based on an alignment of conserved domains. A total of 174 differently expressed TFs (DE-TFs) were increased and 52 DE-TFs were decreased; the biological process-epithelial cell differentiation was inhibited according to the GSEA-GO analysis of TFs; The GO analysis of DE-TFs was enriched in the DNA binding. Protein-protein interaction network (PPI) found 12 hubs, including SMAD4, SMAD2, SMAD3, SP1, GATA2, NR3C1, PPARG, FOXO1, MEF2A, NCOA2, LEF1, and ETS1, which verified genes expression levels by real-time PCR. Conclusions: In this study, SMAD2, PPARG, LEF1, ETS1, GATA2, MEF2A, and NCOA2 are potential candidates that could be targeted by Sr to mediate cell proliferation and differentiation, as well as lipid metabolism. Hence, these results enhance the comprehension of Sr in the regulation of transcription factors and provide new insight into the study of Sr biological function in ruminant animals.

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Identification of common key regulators in rat hepatocyte cell lines under exposure of different pesticides

Cited by 9 publications

References 84 publications

Effect of long‐term treatment with a mixture of pyrethroids on the expression of genes that govern male germ cell production in rats

Effect of long‐term treatment with a mixture of pyrethroids on the expression of genes that govern male germ cell production in rats

Effect of Pesticides on Peroxisome Proliferator-Activated Receptors (PPARs) and Their Association with Obesity and Diabetes

Effect of strontium on transcription factors identified by transcriptome analyses of bovine ruminal epithelial cells

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