Triclosan-induced liver and brain injury in zebrafish (Danio rerio) via abnormal expression of miR-125 regulated by PKCα/Nrf2/p53 signaling pathways

Wang, Caihong; Huang, Wenhao; Lin, Jiebo; Fang, Fang; Wang, Xuedong; Wang, Huili

doi:10.1016/j.chemosphere.2019.125086

Cited by 27 publications

(17 citation statements)

References 56 publications

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“…First, three EDCs (TCS, POP and EE2) act on GPER and/or ERβ to activate the MAPK/ERK pathway, which further results in changes in the expression and phosphorylation of a series of transcription factors. Then, the uncoupled or phosphorylated transcription factors in the cytoplasm are translocated into the nucleus where they bind to the key transcription activity regions of GPER/ERβ to regulate their transcription levels (Lin et al, 2017;Wang et al, 2020). JUND and Arid3a, as well as Arid3a and Foxl1, are coupled transcription factors that bind to the GPER and ERβ transcription activation regions, respectively.…”

Section: Discussionmentioning

confidence: 99%

“…In a toxicological study of EDCs, our previous research observed that different estrogen species produced varying effects on zebrafish (Danio rerio), possibly resulting from differential target and effector organs (Wang et al, 2020). EDCs affect a wide range of physiological processes in reproductive and non-reproductive organs/tissues in zebrafish by means of interaction between estrogen and biomembrane receptors (Saraswat et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

“…Zebrafish are suitable for high throughput toxicological studies due to their high spawning capacity. Zebrafish have been used for decades to assess chemically mediated effects and are generally accepted and recommended for use in evaluating chemical hazards in aquatic environments (Wang et al, 2020;Hamm et al, 2019). In studying gene functions and the toxicity mechanisms of pollutants, they facilitate genetic manipulation by micro-injection in vivo.…”

Section: Introductionmentioning

confidence: 99%

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Identification of receptors for eight endocrine disrupting chemicals and their underlying mechanisms using zebrafish as a model organism

Huang

Lin

et al. 2020

Ecotoxicology and Environmental Safety

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Herein, eight common endocrine disrupting chemicals (EDCs) were exposed to zebrafish (Danio rerio) to investigate the relationship between different EDCs and their activated estrogen receptors. Under acute exposure, we identified five major malformation types whose incidence and deformity modes differed among EDCs. Luciferase analysis divided the EDC receptors into four categories: (i) triclosan (TCS), 17ß-estradiol (E2) and estriol (E3) mainly activated GPER expression; (ii) bisphenol A (BPA), p-(tert-octyl) phenol (POP), 17α-ethynylestradiol (EE2), E2 and E3 activated ERβ expression; (iii) E2 and E3 acted on both GPER and ERβ; and (iv) estrone (E1) and 9,9-bis(4-hydroxyphenyl)fluorene (BHPF) had little effect on the two receptors. In vivo immunofluorescence experiments on 96-hpf larvae provided evidence that TCS and POP acted on GPER and ERβ, respectively, while E2 acted on the two receptors simultaneously. Luciferase activities in the promoter regions of gper (À 986 to À 488) and erβ (À 1998 to À 1496) were higher than those in other regions, identifying these key regions as targets for transcription activity. TCS promoted GPER expression by acting on the JUND transcription factor, while POP promoted ERβ expression by activating the Foxl1 transcription factor. In contrast, E2 mainly regulated transcription of GPER and ERβ by Arid3a. These findings provide compelling evidence that different EDCs possess varying estrogen receptors, leading to differential regulatory pathways and abnormality symptoms. These results offer an experimental strategy and fundamental information to assess the molecular mechanisms of EDC-induced estrogen effects.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Identification of receptors for eight endocrine disrupting chemicals and their underlying mechanisms using zebrafish as a model organism

Huang

Lin

et al. 2020

Ecotoxicology and Environmental Safety

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“…For example, miR-181a can block the differentiation of myeloid cells by inhibiting the expression of adenylate cyclase 9 (AC9), 10 miR-29a and miR-142-3p participate in the regulation of granulocyte/monocyte differentiation, 11 and miR-125b1 can inhibit the phagocytosis and degradation of the promyelocytic leukemia and retinoic acid receptor alpha (PMLRARα) fusion protein via autophagy by regulating the expression of a series of autophagy-related genes, thus inhibiting the differentiation of leukemic cells. 12,13 These results strongly suggest that miRNAs can participate in the differentiation of hematopoietic cells and are closely related to the occurrence and development of AML.…”

Section: Introductionmentioning

confidence: 76%

<p>miR-188-5p Promotes Tumor Growth by Targeting CD2AP Through PI3K/AKT/mTOR Signaling in Children with Acute Promyelocytic Leukemia</p>

Wang

Chen

Ding

et al. 2020

OTT

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Purpose: Pediatric acute promyelocytic leukemia (APL) accounts for 10% of pediatric acute myelogenous leukemia (AML) case and is accompanied by a tendency to hemorrhage. miR-188-5p plays an important role in adult AML. Therefore, the purpose of this study was to explore the effects of miR-188-5p on cell proliferation and apoptosis and tumor growth, and its mechanism in pediatric APL patients. Materials and Methods: Survival-associated miRNAs or mRNAs from TCGA database associated with AML were identified via using the "survival R" package in R language. CCK8, clone formation, flow cytometry, RT-PCR, immunohistochemistry and Western blot assays were used to detect the viability, proliferation, apoptosis, cell cycle, and related gene expression in APL cell lines. The prognostic value of miR-188-5p was evaluated using a ROC curve. The tumorigenic ability of APL cell lines was determined using a nude mouse transplantation tumor experiment. Tumor cell apoptosis was determined by TUNEL assay in vivo. The target genes of miR-188-5p were predicted using the miRDB, miRTarBase, and TargetScan databases. A PPI network was constructed using STRING database and the hub gene was identified using the MCODE plug-in of the Cytoscape software. The DAVID database was used to perform GO and KEGG pathway enrichment analyses. A luciferase reporter assay was used to demonstrate the binding of miR-188-5p to CD2AP. Results: miR-188-5p overexpression or CD2 associated protein (CD2AP) inhibition was significantly associated with poor survival in pediatric APL patients. Upregulation of miR-188-5p was identified in the blood of pediatric APL patients and cell lines. Increased expression of miR-188-5p also promoted the viability, proliferation, and cell cycle progression, and reduced the apoptosis of APL cells. Additionally, upregulation of miR-188-5p regulated the expressions of cyclinD1, p53, Bax, Bcl-2 and cleaved caspase-3. The area under the ROC curve (AUC) of miR-188-5p was 0.661. miR-188-5p overexpression increased the tumorigenic ability of APL and Ki67 expression, and reduced cell apoptosis in vivo. CD2AP was identified as the only overlapping gene from the list of miR-188-5p target genes and survival-related mRNAs of the TCGA database. It was mainly enriched in the "biological process (BP)" and "cellular component (CC)" terms, and was downregulated in the blood of pediatric APL patients and cell lines. The luciferase reporter, RT-PCR, and Western blot assays demonstrated that the binding of miR-188-5p to CD2AP. CD2AP inhibition promoted the proliferation and inhibited the apoptosis of APL cells. Rescue experiments showed that inhibition of miR-188-5p inhibited cell proliferation, activated the PI3K/AKT/mTOR signaling pathway, induced G0/G1 phase arrest, regulated gene expression, and promoted cell apoptosis, which were reversed by CD2AP inhibition.

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“…Target genes of NRF2, such as heme oxygenase-1 (HO-1) or superoxide dismutase (SOD), play a protective role in the pathogenesis of cardiovascular diseases ( Smith et al, 2016 ). PKC promotes nuclear translocation of NRF2 by activating the Ser40 phosphorylation site ( Bloom and Jaiswal, 2003 ; Wang et al, 2020 ). Few studies have been investigated whether NRF2 is involved in PKC activation induced by propofol in myocardial I/R injury.…”

Section: Introductionmentioning

confidence: 99%

Propofol Inhibits Ischemia/Reperfusion-Induced Cardiotoxicity Through the Protein Kinase C/Nuclear Factor Erythroid 2-Related Factor Pathway

Lei

Zhao

et al. 2021

Front. Pharmacol.

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Both hydrogen peroxide (H2O2, H) and ischemia/reperfusion (I/R) can damage cardiomyocytes, which was inhibited by propofol (P). The present research was designed to examine whether propofol can reduce myocardial I/R injury by activating protein kinase C (PKC)/nuclear factor erythroid-2-related factor 2 (NRF2) pathway in H9C2 cells and rat Langendorff models. H9C2 cells were disposed of no reagents (C), H2O2 for 24 h (H), propofol for 1 h before H2O2 (H+P), and chelerythrine (CHE, PKC inhibitor) for 1 h before propofol and H2O2 (H+P+CHE). N = 3. The PKC gene of H9C2 was knocked down by siRNA and overexpressed by phorbol 12-myristate 13-acetate (PMA, PKC agonist). The cell viability and the expressions of PKC, NRF2, or heme oxygenase-1(HO-1) were evaluated. Propofol significantly reduced H9C2 cell mortality induced by H2O2, and significantly increased NRF2 nuclear location and HO-1 expression, which were restrained by siRNA knockout of PKC and promoted by PMA. Rat hearts were treated with KrebsHenseleit solution for 120 min (C), with (I/R+P) or without (I/R) propofol for 20 min before stopping perfusion for 30 min and reperfusion for 60 min, and CHE for 10 min before treated with propofol. N = 6. The levels of lactate dehydrogenase (LDH), superoxide dismutase (SOD), and creatine kinase-MB (CK-MB) in perfusion fluid and antioxidant enzymes in the myocardium were assessed. I/R, which increased LDH and CK-MB expression and reduced SOD expression, boosted the pathological damage and infarcts of the myocardium after reperfusion. However, propofol restrained all these effects, an activity that was antagonized by CHE. The results suggest that propofol pretreatment protects against I/R injury by activating of PKC/NRF2 pathway.

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Triclosan-induced liver and brain injury in zebrafish (Danio rerio) via abnormal expression of miR-125 regulated by PKCα/Nrf2/p53 signaling pathways

Cited by 27 publications

References 56 publications

Identification of receptors for eight endocrine disrupting chemicals and their underlying mechanisms using zebrafish as a model organism

Identification of receptors for eight endocrine disrupting chemicals and their underlying mechanisms using zebrafish as a model organism

<p>miR-188-5p Promotes Tumor Growth by Targeting CD2AP Through PI3K/AKT/mTOR Signaling in Children with Acute Promyelocytic Leukemia</p>

Propofol Inhibits Ischemia/Reperfusion-Induced Cardiotoxicity Through the Protein Kinase C/Nuclear Factor Erythroid 2-Related Factor Pathway

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