Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0700208 (scoliosis)
 8,574 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bisphenol A (BpA) is widely used in industry and dentistry. Its effects on the embryonic development of Xenopus laevis were investigated. Xenopus embryos at stage 10.5 were treated with BpA. Developmental abnormalities were observed at stage 35; malformation of the head region including eyes and scoliosis. The expression of several markers of embryonic development was investigated by reverse transcription-polymerase chain reaction (RT-PCR). The pan-neural marker SOX-2, the neural stem cell marker nrp-1, the mesodermal marker MyoD, and the endodermal marker sox17alpha, were used. Although the expression of marker genes was not changed by treatment with BpA, that of Pax-6, a key regulator of the morphogenesis of the eyes, was decreased by BpA. Pax-6 is a downstream factor of Notch signaling. So, the expression of a typical Notch-dependent factor, ESR-1, was investigated in the presence of BpA. The expression of ESR-1 was efficiently suppressed by BpA. In whole mount in situ hybridization (WISH), Pax-6 was expressed in the central nervous system and eyes. The expression was lost completely on treatment with BpA. The expression of ESR-1 in the central nervous system and eyes also disappeared with BpA treatment. Injection of the intracellular domain of Notch efficiently recovered ESR-1 expression in the presence of BpA although injection of a ligand for notch, Delta, did not. These results suggest that BpA decreased the expression of ESR-1 by disrupting the Notch signal.
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PMID:Bisphenol A causes malformation of the head region in embryos of Xenopus laevis and decreases the expression of the ESR-1 gene mediated by Notch signaling. 1726 83

Bisphenol A (BPA) is being recognized as an endocrine-disrupting chemical (EDC). Recently, several reports indicated that BPA affects the central nervous system (CNS) during embryonic development. However, the molecular mechanism of BPA in the CNS is not well known. Here, we show that BPA affected Notch signaling by inhibiting the activity of the Notch intracellular domain (NICD) cleavage-related enzyme, gamma-secretase (gamma-secretase), at the neurula stage of the Xenopus laevis. BPA caused various morphologic aberrations including scoliosis, eye dysplasia, and loss of pigments in the X. laevis tadpole. These abnormalities were seen whenever BPA was used at the neurula stage. In addition, the expression levels of several marker mRNAs at the neurula stage were investigated by RT-PCR, and we found that the mRNAs expression of ectodermal marker, Pax6, CNS marker, Sox2, and neural crest marker, FoxD3, were decreased by treatment with BPA. These genes contribute to the neural differentiation at the neurula stage, and also the downstream factors of Notch signaling. Injection of NICD but not a Notch ligand, delta 1, rescued the abnormalities caused by BPA. We subsequently assayed the inhibition of the activities of NICD cleavage-related enzymes, tumor necrosis factor alpha converting enzyme, and gamma-secretase, by BPA and found that BPA inhibited the gamma-secretase activity. Furthermore, we expressed presenilin, a main component of gamma-secretase, in Escherichia coli and found the direct binding of BPA with presenilin. These results suggest that BPA affected the neural differentiation by inhibiting gamma-secretase activity, leading to neurodevelopmental abnormalities.
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PMID:Bisphenol A disrupts Notch signaling by inhibiting gamma-secretase activity and causes eye dysplasia of Xenopus laevis. 1921 31