Project description:Tris(1,3-dichloro-2-propyl)phosphate is widely used in consumer products as a flame retardant. Humans are often exposed to this compound. However, the molecular mechanisms of the compound`s adverse effects are still unclear. We address the molecular and cellular mechanisms underlying tris(1,3-dichloro-2-propyl)phosphate effects on HeLa cells. Here RNA-Seq analysis was performed to identify distinct classes of up- or down-regulated genes and their connections to different metabolic pathways.
Project description:Dynamic Alterations in DNA Methylation within Early Zebrafish Embryos Following Exposure to Tris(1,3-dichloro-2-propyl)phosphate or Folic Acid
Project description:Human cell cultures A549 and HepG2/C3 were exposed to 0-100 micromolar Tris(1,3-dichloro-2-propyl)phosphate (TDCIPP) in 0.5% DMSO or to 0.5% DMSO alone for 24 h. RNA was prepared and labeled with Cy3. Agilent SurePrint G3 Human GE v2 8x60k Microarrays, Agilent design ID 039494, were used to profile transcriptional responses to TDCIPP.
Project description:Complex Interplay Among Nuclear Receptors, Cytosine Methylation, and the Metabolome in Driving Tris(1,3-Dichloro-2-Propyl) Phosphate-Induced Epiboly Defects in Zebrafish
Project description:Tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) is a high-production volume organophosphate flame retardant widely used within the United States. Within zebrafish, initiation of TDCIPP exposure at 0.75 h post-fertilization (hpf) results in genome-wide alterations in methylation during cleavage (2 hpf) as well as epiboly delay or arrest (at higher concentrations) during late-blastula and early-gastrula (4-6 hpf). To determine whether these TDCIPP-induced effects were associated with impacts on the transcriptome, embryos were exposed to vehicle (0.1% DMSO) or 2 μM TDCIPP from 0.75 hpf to 6 hpf, and total RNA was extracted from triplicate embryo pools per treatment and hybridized onto duplicate Affymetrix Zebrafish Gene 1.0 ST Arrays per RNA sample. Based on transcriptome-wide profiling, TDCIPP resulted in a significant impact on biological pathways involved in dorsoventral patterning and bone morphogenetic protein (BMP) signaling. Consistent with pathway-level responses, TDCIPP exposure also resulted in strongly dorsalized embryos by 24 hpf – a phenotype that mimicked the effects of dorsomorphin, a potent and selective BMP inhibitor. Moreover, the majority of dorsalized embryos were preceded by epiboly arrest at 6 hpf. Our microarray data also revealed that the expression of sizzled (szl) – a gene encoding a secreted Frizzled-related protein that limits BMP signaling – was significantly decreased by nearly 4-fold at 6 hpf. Therefore, we used a splice-blocking morpholino to test the hypothesis that knockdown of szl phenocopies TDCIPP-induced delays in epiboly progression. Interestingly, contrary to our hypothesis, injection of szl MOs did not affect epiboly progression but, similar to chordin (chd) morphants, resulted in mildly ventralized embryos by 24 hpf. Overall, our findings suggest that TDCIPP-induced epiboly delay may be independent of szl expression and function, and that TDCIPP-induced dorsalization may – similar to dorsomorphin – be due to interference with BMP signaling during early zebrafish.
Project description:Alzheimer's disease is the most common form of dementia characterized on cognitive impairment. Autophagy-lysosome dysfunction is linked to AD pathology. Tris (1,3-dichloro-2-propyl) phosphate (TDCIPP) is a widely used organophosphorus flame retardants with the potential to induce neuronal damage. We found that TDCIPP significantly increased expression of BACE1 and of Aβ42. TMT labeled proteomic study were used to reveal profile changes of N2a-APPswe cells after exposure by TDCIPP. Proteomic and bioinformatic analysis revealed that lysosomal proteins were dysregulated after TDCIPP treatment in N2a-APPswe cells. LC3, P62, CTSD, and LAMP1 were increased, while STAT1 was decreased after TDCIPP exposure and dysregulated proteins were validated by Western blotting. Our results, for the first time revealed that TDCIPP could be one of potential environment risk factors for AD development. Autophagy dysregulation may take an important role on TDCIPP induced Aβ42 production.
Project description:Mussels (Mytilus galloprovincialis) were exposed during 7 and 28 days in seawater (control), seawater + acetone (solvent control, SC), and 10 micrograms per Litre of tris(1,3-dichloro-2-propyl) phosphate (TDCPP). TDCPP was added from a stock solution prepared in acetone, the volume added being 100 µL per 30 L aquaria. The same volume of acetone was added to SC aquaria. Mussel density was 20 mussels per each 30 L aquaria at the beginning of the experiment and varied between 15 ‒ 20 mussels/30 L aquaria during the 28 days exposure period. Exposure conditions were the following: T = 15.6 ± 0.7 ºC, S = 35.5 ± 0.5 ppt, pH = 7.9 ± 0.1, O2 = 7.9 ± 0.6 mg L-1 and 10:14h light:dark photoperiod. Water was renewed twice per week and mussels were fed before every water renewal with a mixture of phytoplankton representing 1% of mussel tissue dry weight.