Increased, Hepatic thyroid hormone uptake/transport

115-86-6

XZZNDPSIHUTMOC-UHFFFAOYSA-N

Triphenyl phosphate

Phosphoric acid, triphenyl ester Celluflex TPP Disflamoll TP fosfato de trifenilo NSC 57868 Phenyl phosphate Phoscon FR 903N Phosflex TPP Phosphate de triphenyle Reofos TPP Sumilizer TPP Triphenoxyphosphine oxide Triphenylphosphat Triphenylphosphate Wako TPP

DTXSID1021952

CHEBI:60311

CHEBI thyroid hormone

PR:000029191

PR cell cycle-related cyclin

GO:0006810

GO transport

GO:0051726

GO regulation of cell cycle

GO:0006915

GO apoptotic process

WIKI increased

WIKI disrupted

Triphenyl phosphate

2020-03-30T16:54:36

WCS_8355

common ecological species African clawed frog

9606

NCBI Homo sapiens

10090

NCBI Mus musculus

10116

NCBI Rattus norvegicus

6239

NCBI Caenorhabditis elegans

Increased, Hepatic thyroid hormone uptake/transport

Tissue

CL:0000182

CL hepatocyte

Not Specified

AOPWiki 2016-11-29T18:41:30

2017-09-16T10:17:31

Cell cycle, disrupted

Cellular

The disruption of the cell cycle leads to a decrease in cell number. The cell cycle consists of G1, S, G2, M, and G0 phases. The cell cycle regulation is disrupted by the cell cycle arrest in certain cell cycle phases. The histone gene expression is regulated in cell cycle phases [Heintz et al., 1983].

The percentage of cells at G1, G0, S, and G2/M phases can be detected by flow cytometry  [Li et al., 2013]. Cell cycle distribution was analyzed by fluorescence-activated cell sorter (FACS) analysis with a Partec PAS-II sorter [Zupkovitz et al., 2010]. The four cell-cycle phases in living cells can be measured with four-color fluorescent proteins using live-cell imaging [Bajar et al., 2016]. The incorporation of [3H]deoxycytidine or [3H]thymidine into cell DNA during the S phase can be monitored as DNA synthesis [Heintz et al., 1982].

The histone gene expression alters in each phase of the cell cycle in human HeLa cells (Homo sapiens) [Heintz et al., 1982].

UBERON:0000062

UBERON organ

CL:0000000

CL cell

High Unspecific

Moderate

Not Otherwise Specified

High High

Bajar, B.T. et al. (2016), "Fluorescent indicators for simultaneous reporting of all four cell cycle phases", Nat Methods 13:993-996  Heintz, N. et al. (1983), "Regulation of human histone gene expression: Kinetics of accumulation and changes in the rate of synthesis and in the half-lives of individual histone mRNAs during the HeLa cell cycle", Molecular and Cellular Biology 3:539-550 Li, Q. et al. (2013), "Glyphosate and AMPA inhibit cancer cell growth through inhibiting intracellular glycine synthesis", Drug Des Devel Ther 7:635-643 AOPWiki 2018-01-21T20:59:13

2021-06-30T02:56:39

systemic inflammatory response syndrome

SIRS

Individual

AOPWiki 2021-03-19T09:50:36

2021-03-19T09:50:36

Increase cell proliferation

Cellular

AOPWiki 2018-12-19T11:25:40

2018-12-19T11:25:40

Apoptosis

Cellular

Apoptosis, the process of programmed cell death, is characterized by distinct morphology with DNA fragmentation and energy dependency [Elmore, 2007]. Apoptosis, also called “physiological cell death”, is involved in cell turnover, physiological involution, and atrophy of various tissues and organs [Kerr et al., 1972]. The formation of apoptotic bodies involves marked condensation of both nucleus and cytoplasm, nuclear fragmentation, and separation of protuberances [Kerr et al., 1972]. Apoptosis is characterized by DNA ladder and chromatin condensation. Several stimuli such as hypoxia, nucleotides deprivation, chemotherapeutical drugs, DNA damage, and mitotic spindle damage induce p53 activation, leading to p21 activation and cell cycle arrest [Pucci et al., 2000]. The SAHA or TSA treatment on neonatal human dermal fibroblasts (NHDFs) for 24 or 72 hrs inhibited proliferation of the NHDF cells [Glaser et al., 2003]. Considering that the acetylation of histone H4 was increased by the treatment of SAHA for 4 hrs, histone deacetylase inhibition may be involved in the inhibition of the cell proliferation [Glaser et al., 2003]. The impaired proliferation was observed in HDAC1-/- ES cells, which was rescued with the reintroduction of HDAC1 [Zupkovitz et al., 2010]. The present AOP focuses on the p21 pathway leading to apoptosis, however, alternative pathways such as NF-kappaB signaling pathways may be involved in the apoptosis of spermatocytes [Wang et al., 2017].

Apoptosis is characterized by many morphological and biochemical changes such as homogenous condensation of chromatin to one side or the periphery of the nuclei, membrane blebbing and formation of apoptotic bodies with fragmented nuclei, DNA fragmentation, enzymatic activation of pro-caspases, or phosphatidylserine translocation that can be measured using electron and cytochemical optical microscopy, proteomic and genomic methods, and spectroscopic techniques [Archana et al., 2013; Martinez et al., 2010; Taatjes et al., 2008; Yasuhara et al., 2003]. ・DNA fragmentation can be quantified with comet assay using electrophoresis, where the tail length, head size, tail intensity, and head intensity of the comet are measured [Yasuhara et al., 2003]. ・The apoptosis is detected with the expression alteration of procaspases 7 and 3 by Western blotting using antibodies [Parajuli et al., 2014]. ・The apoptosis is measured with down-regulation of anti-apoptotic gene baculoviral inhibitor of apoptosis protein repeat containing 2 (BIRC2, or cIAP1) [Parajuli et al., 2014]. ・Apoptotic nucleosomes are detected using Cell Death Detection ELISA kit, which was calculated as absorbance subtraction at 405 nm and 490 nm [Parajuli et al., 2014]. ・Cleavage of PARP is detected with Western blotting [Parajuli et al., 2014]. ・Caspase-3 and caspase-9 activity is measured with the enzyme-catalyzed release of p-nitroanilide (pNA) and quantified at 405 nm [Wu et al., 2016]. ・Apoptosis is measured with Annexin V-FITC probes, and the relative percentage of Annexin V-FITC-positive/PI-negative cells is analyzed by flow cytometry [Wu et al., 2016]. ・Apoptosis is detected with the Terminal dUTP Nick End-Labeling (TUNEL) method to assay the endonuclease cleavage products by enzymatically end-labeling the DNA strand breaks [Kressel and Groscurth, 1994]. ・For the detection of apoptosis, the testes are fixed in neutral buffered formalin and embedded in paraffin. Germ cell death is visualized in testis sections by Terminal dUTP Nick End-Labeling (TUNEL) staining method [Wade et al., 2008]. The incidence of TUNEL-positive cells is expressed as the number of positive cells per tubule examined for one entire testis section per animal [Wade et al., 2008]. <ul> <li>Apoptosis is detected with the Annexin V test</li> </ul>

・Apoptosis is induced in human prostate cancer cell lines (Homo sapiens) [Parajuli et al., 2014]. ・Apoptosis occurs in B6C3F1 mouse (Mus musculus) [Elmore, 2007]. ・Apoptosis occurs in Sprague-Dawley rat (Rattus norvegicus) [Elmore, 2007]. ・Apoptosis occurs in the nematode (Caenorhabditis elegans) [Elmore, 2007]. <ul> <li>Apoptosis occurs in breast cancer cells, human and mouse</li> </ul>

UBERON:0000062

UBERON organ

CL:0000000

CL cell

High Unspecific

High

Not Otherwise Specified

High High High High

Archana, M. et al. (2013), "Various methods available for detection of apoptotic cells", Indian J Cancer 50:274-283 Elmore, S. (2007), "Apoptosis: a review of programmed cell death", Toxicol Pathol 35:495-516 Glaser, K.B. et al. (2003), "Gene expression profiling of multiple histone deacetylase (HDAC) inhibitors: defining a common gene set produced by HDAC inhibition in T24 and MDA carcinoma cell lines", Mol Cancer Ther 2:151-163 Kerr, J.F.R. et al. (1972), "Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics", Br J Cancer 26:239-257 Kressel, M. and Groscurth, P. (1994), "Distinction of apoptotic and necrotic cell death by in situ labelling of fragmented DNA", Cell Tissue Res 278:549-556 Martinez, M.M. et al. (2010), "Detection of apoptosis: A review of conventioinal and novel techniques", Anal Methods 2:996-1004 Parajuli, K.R. et al. (2014), "Methoxyacetic acid suppresses prostate cancer cell growth by inducing growth arrest and apoptosis", Am J Clin Exp Urol 2:300-313 Pucci, B. et al. (2000), "Cell cycle and apoptosis", Neoplasia 2:291-299 Taatjes, D.J. et al. (2008), "Morphological and cytochemical determination of cell death by apoptosis", Histochem Cell Biol 129:33-43 Wade, M.G. et al. (2008), "Methoxyacetic acid-induced spermatocyte death is associated with histone hyperacetylation in rats", Biol Reprod 78:822-831 Wang, C. et al. (2017), "CD147 regulates extrinsic apoptosis in spermatocytes by modulating NFkB signaling pathways", Oncotarget 8:3132-3143 Wu, R. et al. (2016), "microRNA-497 induces apoptosis and suppressed proliferation via the Bcl-2/Bax-caspase9-caspase 3 pathway and cyclin D2 protein in HUVECs", PLoS One 11:e0167052 Yasuhara, S. et al. (2003), "Comparison of comet assay, electron microscopy, and flow cytometry for detection of apoptosis", J Histochem Cytochem 51:873-885 Zupkovitz, G. et al. (2010), "The cyclin-dependent kinase inhibitor p21 is a crucial target for histone deacetylase 1 as a regulator of cellular proliferation", Mol Cell Biol 30:1171-1181 AOPWiki 2017-02-07T13:21:50

2022-12-20T08:33:23

Altered, Thyroid hormone-dependent gene expression

Altered, TH-dependent gene expression

Molecular

Not Specified AOPWiki 2020-12-09T14:22:38

2020-12-09T14:22:38

AOP for thyroid disorder caused by triphenyl phosphate via TRβ activation

Thyroid hormone effect

Brendan Ferreri-Hanberry

Xiaoqing Wang, Fei Li*, Jingwen Chen, Chenglong Ji, Huifeng Wu <quillbot-extension-portal></quillbot-extension-portal>

BY-SA

2.0

The critical molecular initiating event (MIE) was the configuration changes of C-terminal helix 12 (H12) of thyroid hormone receptor β (TRβ) induced by triphenyl phosphate (TPP) binding. The transcriptomic analysis extended the related key event (KE1) at the subcellular level, such as changes in gene expression levels for coding cycle regulation (CCND1), inflammatory response (IL1A and IL6), and cell proliferation and apoptosis (BAD, TP53 and CASP9). Then, the KE2 at cellular levels such as apoptosis, cell cycle control, and cell proliferation were influenced accordingly. As a result, these alterations led to thyroid disorder as adverse outcomes. <quillbot-extension-portal></quillbot-extension-portal> A large number of studies reported that triphenyl phosphate (TPP) was detected from environmental and human samples, indicating potential environmental and health risks. Previous toxicology researches suggested that TPP was a potential endocrine disruptor, which was harmful to thyroid function . However, the potential thyroid hormone-disrupting effects of TPP were scarce and the mechanism remained unclear. Additional studies are required to further explore the toxicity pathway of thyroid dysfunction exposed by TPP. <quillbot-extension-portal></quillbot-extension-portal>

This study retrieved the data from comparative toxicogenomics database (CTD) and screened out the core gene. Molecular dynamics (MD) analysis was used to explore configuration changes and confirm molecular initiating event (MIE). The transcriptomic analysis was further utilized to supplement the relationships between MIEs and key events (KEs) of AOP. <quillbot-extension-portal></quillbot-extension-portal>

<quillbot-extension-portal></quillbot-extension-portal>   <quillbot-extension-portal></quillbot-extension-portal>

<quillbot-extension-portal></quillbot-extension-portal>

<div> <table class="table table-bordered table-fullwidth"> <thead> <tr> <th>Modulating Factor (MF)</th> <th>Influence or Outcome</th> <th>KER(s) involved</th> </tr> </thead> <tbody> <tr> <td> </td> <td> </td> <td> </td> </tr> </tbody> </table> </div> <quillbot-extension-portal></quillbot-extension-portal>

<quillbot-extension-portal></quillbot-extension-portal>

Not Specified

<quillbot-extension-portal></quillbot-extension-portal> AOPWiki 2021-04-21T21:08:37

2023-09-25T16:27:07