Transcriptomics

Dataset Information

0

Comparison of Bzrp ligands


ABSTRACT: This series compares the effects that two pharmacologically distinct ligands at the mitochondrial peripheral-type benzodiazepine receptor (Bzrp). PK11195 (4.0 mg/kg, a presumed antagonist) has no observable adverse effects in pregnant mice on either 8 days post-coitus (d.p.c.) or 9 d.p.c. Furthermore, PK11195 is shown to rescue mouse fetuses from microphthalmia or microphthalmia-microcephaly induced with 2CdA or MeHg, respectively; effects of PK11195 on EtOH-induced craniofacial malformations are not yet unkown. Ro5-4864 (4.0 mg/kg, a presumed agonist) is weakly teratogenic on 8 d.p.c. (effects on 9 d.p.c. unknown) and this Bzrp ligand does not rescue fetuses from malformations induced with either 2CdA or MeHg; effects of Ro5-4864 on EtOH-induced craniofacial malformations is unknown for either sensitive (C57BL/6J) or insensitive (C57BL/6N) strains. The 4.0 mg/kg dose of Bzrp ligands is consistent with pharmacological activity in several studies. Pregnant mice were exposed to these agents on 8 d.p.c. (2CdA, EtOH) or 9 d.p.c. (MeHg). The test dose of 2.5 mg/kg 2CdA was modeled for a 5% increased risk of microphthalmia in term fetuses. Full remediation with PK11195 anticipated. The test dose of 5.0 mg/kg MeHg gives an estimated 20% increased risk of microphthalmia-microcephaly (encephalopathy) in term fetuses. Partial remediation with PK11195 is anticipated to <10% malformations. Again the effects of PK11195 on EtOH teratogenicity is not yet known. The sampling time was chosen as the time of p53 protein induction (3.0h to 4.5h post-treatment). Whereas co-treatment with PK11195 suppresses embryonic p53 protein induction Ro5-4864 does not block this reaction. All measurements were on RNA from the embryonic headfold (8 d.p.c.) or prosencephalon (9 d.p.c.). Keywords = peripheral benzodiazepine receptor Keywords = Bzrp ligands Keywords = PK11195 Keywords = Ro5-4864 Keywords = embryo Keywords = p53 protein induction Keywords: ordered

ORGANISM(S): Mus musculus

PROVIDER: GSE1072 | GEO | 2004/03/11

SECONDARY ACCESSION(S): PRJNA87165

REPOSITORIES: GEO

Dataset's files

Source:
Action DRS
Other
Items per page:
1 - 1 of 1

Similar Datasets

2010-06-09 | E-GEOD-1072 | biostudies-arrayexpress
2004-03-11 | GSE1077 | GEO
2004-03-11 | GSE1070 | GEO
2004-03-11 | GSE1075 | GEO
2010-06-09 | E-GEOD-1079 | biostudies-arrayexpress
2004-03-11 | GSE1079 | GEO
2004-03-11 | GSE1076 | GEO
2004-03-11 | GSE1068 | GEO
2004-03-11 | GSE1069 | GEO
2004-03-11 | GSE1074 | GEO