title: Apoptosis and gene expression in the developing mouse brain of fusarenon-X-treated pregnant mice.
abstract: Fusarenon-X (FX), a type B trichothecene mycotoxin, is mainly produced by Fusarium crookwellense, which occurs naturally in agricultural commodities, such as wheat and barley. FX has been shown to exert a variety of toxic effects on multiple targets in vitro. However, the embryonic toxicity of FX in vivo remains unclear. In the present study, we investigated FX-induced apoptosis and the relationship between the genetic regulatory mechanisms and FX-induced apoptosis in the developing mouse brain of FX-treated pregnant mice. Pregnant mice were orally administered FX (3.5 mg/kg b.w.) and were assessed at 0, 12, 24 and 48 h after treatment (HAT). Apoptosis in the fetal brain was determined using hematoxylin and eosin staining, the TUNEL method, immunohistochemistry for PCNA and electron microscopy. Gene expressions were evaluated using microarray and real time-reverse transcription polymerase chain reaction (qRT-PCR). Histopathological changes showed that the number of apoptotic cells in the telencephalon of the mouse fetus peaked at 12 HAT and decreased at 24 and 48 HAT. FX induced the up-regulation of Bax, Trp53 and Casp9 and down-regulated Bcl2 but the expression levels of Fas and Casp8 mRNA remained unchanged. These data suggested that FX induces apoptosis in the developing mouse brain in FX-treated dams. Moreover, the genetic regulatory mechanisms of FX-induced apoptosis are regulated by Bax, Bcl2, Trp53 and Casp9 or can be defined via an intrinsic apoptotic pathway.
authors.affiliation: Department of Pharmacology, Faculty of Veterinary Medicine, Kasetsart University, Bangkok 10900, Thailand.
authors.forename: Samak
authors.initials: S
authors.lastname: Sutjarit
authors.affiliation: Department of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 0600818, Japan.
authors.forename: Shota M M
authors.initials: SM
authors.lastname: Nakayama
authors.affiliation: Department of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 0600818, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Ikenaka
authors.affiliation: Department of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 0600818, Japan.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Ishizuka
authors.affiliation: Department of Pathology, Faculty of Veterinary Science, Chulalongkorn University, Bangkok 10330, Thailand.
authors.forename: Wijit
authors.initials: W
authors.lastname: Banlunara
authors.affiliation: Faculty of Veterinary Technology, Kasetsart University, Bangkok 10900, Thailand.
authors.forename: Worawut
authors.initials: W
authors.lastname: Rerkamnuaychoke
authors.affiliation: Research Center for Food Safety, University of Tokyo, Tokyo 1138657, Japan.
authors.forename: Susumu
authors.initials: S
authors.lastname: Kumagai
authors.affiliation: Interdisciplinary Graduate Program in Genetic Engineering, Graduate School, Kasetsart University, Bangkok 10900, Thailand; Department of Pharmacology, Faculty of Veterinary Medicine, Kasetsart University, Bangkok 10900, Thailand. Electronic address: fvetamp@ku.ac.th.
authors.forename: Amnart
authors.initials: A
authors.lastname: Poapolathep
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis / Q000235:genetics; D001921:Brain / Q000187:drug effects / Q000196:embryology / Q000254:growth & development*; D001923:Brain Chemistry / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis / Q000302:isolation & purification; D053938:DNA Fragmentation / Q000187:drug effects; D004587:Electrophoresis, Agar Gel; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D008813:Mice, Inbred ICR; D046228:Microarray Analysis; D008854:Microscopy, Electron; D009183:Mycotoxins / Q000633:toxicity*; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D012313:RNA / Q000096:biosynthesis / Q000235:genetics; D059467:Transcriptome / Q000187:drug effects; D014255:Trichothecenes / Q000633:toxicity*
chemical_list: D051017:Apoptosis Regulatory Proteins; D009183:Mycotoxins; D018809:Proliferating Cell Nuclear Antigen; D014255:Trichothecenes; C002469:fusarenon-X; D012313:RNA; D004247:DNA
keywords: Apoptosis; Fusarenon-X; Gene expression profiling; Mouse fetal brain