RESUMEN
Gestational cadmium exposure increases the risk of preeclampsia. Placenta mitophagy was activated in preeclampsia. The aim of present study was to explore the mechanism of cadmium-induced mitophagy activation and its association with preeclampsia. Mitophagy markers expression levels were detected by quantitative real-time PCR, Western blot, immunofluorescence and immunochemistry in preeclampsia placenta. JEG3 cells were treated with CdCl2, iopanoic acid (IOP), 3-methyladenine and PGC1α SiRNA to verify mechanism of cadmium-induced mitophagy. Mitophagy marker LC3BII/I and P62 expression were increased and mitochondrial membrane receptor protein TOM20 and FUNDC1 expression were decreased in preeclampsia placenta as compared with that in normotension control. Mitophagy marker LC3BII/I and P62 expression were increased and TOM20 and FUNDC1 expression was decreased in CdCl2-treated JEG3 cells. Meanwhile, mitochondrial biogenesis regulator, PGC1α expression was decreased in preeclampsia and CdCl2-treated JEG3 cells. The expressions of LC3B and P62 were increased and the expressions of TOM20, FUNDC1 and PGC1α were decreased in IOP-treated cell. PGC1α SiRNA transfection led to increased expression of LC3BII/I and P62 and decreased expression of TOM20 and FUNDC1. The expression of sFlt1 was increased in preeclampsia placenta, CdCl2-treated cells, in IOP-treated cells and in PGC1α SiRNA transfected cells. 3-methyladenine treatment protected the increased expression of sFlt1 in CdCl2-treated cells, in IOP-treated cells and in PGC1α SiRNA transfected cells. Meanwhile, co-treatment of cadmium and IOP or PGC1αSiRNA led to a reduce expressions of OPA1, MFN1, MFN2 and FUNDC1 as compared to cadmium-treated, IOP-treated and PGC1α SiRNA-treated cells. These results elucidated that maternal cadmium exposure activated placenta mitophagy through downregulation of thyroid hormone receptor signal mediated decreased expression of PGC1α and was associated with the occurrence of preeclampsia.
Asunto(s)
Mitofagia , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma , Placenta , Preeclampsia , Receptores de Hormona Tiroidea , Humanos , Preeclampsia/inducido químicamente , Femenino , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismo , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/genética , Embarazo , Mitofagia/efectos de los fármacos , Placenta/efectos de los fármacos , Placenta/metabolismo , Receptores de Hormona Tiroidea/genética , Receptores de Hormona Tiroidea/metabolismo , Cadmio/toxicidad , Regulación hacia Abajo/efectos de los fármacos , Adulto , Transducción de Señal/efectos de los fármacosRESUMEN
Enterovirus 71 (EV71) is the main pathogenic virus that causes hand, foot, and mouth disease (HFMD). Studies have reported that EV71-induced infections including aseptic meningitis, acute flaccid paralysis, and even neurogenic pulmonary edema, can progress to severe neurological complications in infants, young children, and the immunosuppressed population. However, the mechanisms through which EV71 causes neurological diseases have not been fully explored. Non-coding RNAs (ncRNAs), are RNAs that do not code for proteins, play a key role in biological processes and disease development associated with EV71. In this review, we summarized recent advances concerning the impacts of ncRNAs on neurological diseases caused by interaction between EV71 and host, revealing the potential role of ncRNAs in pathogenesis, diagnosis and treatment of EV71-induced neurological complications.
