No abstract

Proinflammatory cytokines such as TNF-alpha and IL-1beta lead to downregulation of hepatic organic anion transporters in cholestasis. This adapted response is transcriptionally mediated by nuclear hormone receptors and liver-specific transcription factors. Because little is known in vivo about cytokine-dependent regulatory events, mice were treated with either TNF-alpha or IL-1beta for up to 16 h. Transporter mRNA expression was determined by Northern blot analysis, nuclear activity, and protein-expression of transactivators by EMSA and Western blotting. TNF-alpha induces a sustained decrease in Ntcp, Oatp1/Oatp1a1, and Bsep mRNA expression but exerts only transient [multidrug resistance-associated protein 2 (Mrp2)] or no effects (Mrp3) on Mrps. In addition to Ntcp and Oatp1/Oatp1a1, IL-1beta also downregulates Bsep, Mrp2, and Mrp3 mRNAs to some extent. To study transcriptional regulation, Ntcp and Bsep promoters were first cloned from mice revealing a new distal Ntcp hepatocyte nuclear factor 1 (HNF-1) element but otherwise show a conserved localization to known rat regulatory elements. Changes in transporter-expression are preceeded by a reduction in binding activities at IR-1, ER-8, DR-5, and HNF-1alpha sites after 4 h by either cytokine, which remained more sustained by TNF-alpha in the case of nuclear receptors. Nuclear protein levels of retinoid X receptor (RXR)-alpha are significantly decreased by TNF-alpha but only transiently affected by IL-1beta. Minor reductions of retinoic acid receptor, farnesoid X receptor, pregnane X receptor, and constitutive androstane receptor nuclear proteins are restricted to 4 h after cytokine application and paralleled by a decrease in mRNA levels. Basolateral and canalicular transporter systems are downregulated by both cytokines, TNF-alpha and IL-1beta. Activity of HNF-1alpha as regulator of mNtcp is suppressed by both cytokines. Decreased binding activities of nuclear receptor heterodimers may be explained by a reduction of the ubiquitous heterodimerization partner RXR-alpha.

The thermal stability of nano-silicon electrodes before and after lithiation was studied by means of differential scanning calorimetry (DSC). It was found that pristine Si electrodes heated in presence of EC/DEC 1M LiPF 6 electrolyte show exothermic reactions between sodium carboxymethylcellulose (Na CMC binder) and LiPF 6 . The products of thermal decomposition of a lithiated nano-Si electrode with electrolyte at different temperatures were identified using attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR). SEI layer was found to be responsible for the thermal reactions in the range between 77 and 107 • C. Exothermic events between 107 and 140 • C were caused by partial decomposition of LiPF 6 salt, which products initiated further transformations of SEI layer compounds and esterification of Na CMC. Interaction between nano-Li x Si and EC/DEC 1M LiPF 6 was the reason for the main exothermic peaks at temperatures between 150 and 300 • C. Nano-Li x Si heated with EC/DEC solvent mixture without LiPF 6 resulted in electrolyte decomposition at much lower temperatures (>105 • C). Therefore, the important role of LiPF 6 in the thermal stabilization of nano-Li x Si with electrolyte at temperatures <140 • C was confirmed while LiTFSI salt added to EC/DEC was ineffective in the prevention of the main exothermic reaction starting at 105 • C.

No abstract