title: Sirtuin inhibitor Ex-527 causes neural tube defects, ventral edema formations, and gastrointestinal malformations in Xenopus laevis embryos.
abstract: Chemical reagent Ex-527 is widely used as a major inhibitor of Sirtuin enzymes, which are a family of highly conserved protein deacetylases and have been linked with caloric restriction and aging by modulating energy metabolism, genomic stability, and stress resistance. However, the extent to which Ex-527 controls early developmental events of vertebrate embryos remains to be understood. Here, we report an examination of Ex-527 effects during Xenopus early development, followed by a confirmation of expressions of xSirt1 and xSirt2 in embryonic stages and enhancement of acetylation by Ex-527. First, we found that reductions in size of neural plate at neurula stages were induced by Ex-527 treatment. Second, tadpoles with short body length and large edematous swellings in the ventral side were frequently observed. Moreover, Ex-527-treated embryos showed severe gastrointestinal malformations in late tadpole stages. Taken together with these results, we conclude that the Sirtuin family start functioning at early embryonic stages and is required for various developmental events.
authors.affiliation: Graduate School of Science and Technology, Shizuoka University, 836 Ohya, Suruga-ku, Shizuoka, 422-8529, Japan.
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Ohata
authors.forename: Shinya
authors.initials: S
authors.lastname: Matsukawa
authors.forename: Yuki
authors.initials: Y
authors.lastname: Moriyama
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Michiue
authors.forename: Kenta
authors.initials: K
authors.lastname: Morimoto
authors.forename: Yuka
authors.initials: Y
authors.lastname: Sato
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kuroda
mesh_terms: D000818:Animals; D002227:Carbazoles / Q000633:toxicity*; D004487:Edema / Q000139:chemically induced*; D004625:Embryo, Nonmammalian / Q000187:drug effects*; D041981:Gastrointestinal Tract / Q000002:abnormalities* / Q000196:embryology; D009436:Neural Tube Defects / Q000139:chemically induced* / Q000196:embryology; D037761:Sirtuins / Q000037:antagonists & inhibitors*; D014982:Xenopus laevis / Q000196:embryology*
chemical_list: C550547:6-chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxamide; D002227:Carbazoles; D037761:Sirtuins
keywords: Ex-527; Sirtuin; Xenopus; teratogenesis