RESUMEN
As is ubiquitous in the environmental sources, benzo(a)pyrene (BaP) has been reported to induce reprotoxicity in previous studies. Toxicity to trophoblast cells may be one key factor, but evidences were absent. We speculated that BaP can induce cytotoxicity in human trophoblast HTR-8/SVneo (HTR) cells, and Schisandrin B (Sch B) as a potential protector can inhibit the cytotoxicity. MTS assay identified that BaP induced HTR cells death while Sch B played a cytoprotective role. And after Nrf2 interference, the ability of Sch B-induced cytoprotection was declined. Furthermore, PCR, western blot, ELISA, and SOD assays were found that Sch B significantly increased the mRNA and protein expression of Nrf2, HO1, NQO1, and SOD in the Nrf2-ARE pathway, and the extents of increase were declined after Nrf2 interference. These results demonstrated that the Nrf2-ARE pathway plays an important role in Sch B attenuating BaP-induced HTR cells damages in vitro. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1439-1449, 2016.
Asunto(s)
Benzo(a)pireno/antagonistas & inhibidores , Citoprotección , Lignanos/farmacología , Factor 2 Relacionado con NF-E2/fisiología , Compuestos Policíclicos/farmacología , Trofoblastos/efectos de los fármacos , Elementos de Respuesta Antioxidante/efectos de los fármacos , Benzo(a)pireno/toxicidad , Línea Celular , Ciclooctanos/farmacología , Femenino , Humanos , Factor 2 Relacionado con NF-E2/antagonistas & inhibidores , Factor 2 Relacionado con NF-E2/genética , ARN Interferente Pequeño/genética , Transducción de Señal/efectos de los fármacos , Transducción de Señal/genética , Trofoblastos/fisiologíaRESUMEN
Long-term exposure to fine particulate matter (PM2.5) may cause adverse pregnancy outcomes but the mechanisms are not clear. Our research confirms that PM2.5 induced DNA damage, and inhibited cell proliferation in HTR-8/SVneo cells, presenting in a dose- and time-dependent manners. Using quantitative proteomics, the 182 and 486 differentially expressed proteins in cells treated with 120µgml-1 PM2.5 for 24 and 48h were involved in many critical biological processes, including of cell proliferation, response to DNA damage, regulation of small GTPase mediated signal transduction, and etc. Further validation indicated that PM2.5 blocked the cell cycle at the G2/M phase through activation of the ATR-Cyclin E1/Cdk6 pathway, and it reduced the migration and invasion by upregulating TIMP1 and TIMP2 expression and downregulating Collagen I expression. Our findings were consistent with the observed effects of PM2.5 on cell cycle arrest and inhibition of migration and invasion in human extravillous trophoblast.