Purpose: MetS consist of five risk factors: elevated blood pressure and fasting glucose, visceral obesity, dyslipidemia and hypercholesterinemia. The physiological impact of lipid metabolism indicated as visceral obesity and hepatic lipid accumulation is still under debate. One major cause of disturbed lipid metabolism might be dysfunction of cellular organelles controlling energy homeostasis, i.e. mitochondria and peroxisomes.
Alteration of Liver Peroxisomal and Mitochondrial Functionality in the NZO Mouse Model of Metabolic Syndrome.
Sex, Age, Specimen part
View SamplesHTETOP cells, derived from the human fibrosarcoma cell line HT1080, express human topoisomearse II (TOP2A) exclusively from a tetracycline (TET)-regulated transgene, we used HTETOP cells to differentiate between TOP2A-dependent and independent apoptotic effects of doxorubicin and dexrazoxane.
Topoisomerase II{alpha}-dependent and -independent apoptotic effects of dexrazoxane and doxorubicin.
Cell line
View SamplesMS-275 and hydroxyurea treatment influences whole gene expression including DNA damage response and cell cycle checkpoint signaling.
HDAC1 and HDAC2 integrate checkpoint kinase phosphorylation and cell fate through the phosphatase-2A subunit PR130.
Specimen part, Cell line
View SamplesPregnane X receptor (PXR) is generally considered the most important sensor of natural and anthropogenic xenobiotics in vertebrates. In Xenopus, however, PXR plays a role in neural development and it is irresponsive to xenobiotics. We report a first broad-spectrum amphibian xenobiotic receptor, which is an ortholog of the mammalian constitutive androstane receptor (CAR). The low basal activity and pronounced responsiveness to activators such as drugs and steroids displayed by the Xenopus CAR resemble PXR, which both trace back to a common ancestor early in the divergence of land vertebrates. The constitutive activity of CAR emerged first in Sauropsida (reptiles and birds) and it is common to all fully terrestrial land vertebrates (Amniota). This activity can be mimicked by humanizing just two amino acids of the Xenopus CAR. These results demonstrate a remarkable plasticity of CAR which enabled its employment as Xenopus xenosensors. They open way to toxicogenomic and bioaugmentation studies in amphibians, a critically endangered taxon of land vertebrates. Taken together, we provide evidence for a much earlier origin of CAR, for its conservation in tetrapods which exceeds that of PXR, and for its remarkable functional plasticity which enabled its role as a PXR-like xenosensor in Amphibia.
Evolutionary history and functional characterization of the amphibian xenosensor CAR.
Sex, Specimen part, Treatment
View Samples