[show abstract][hide abstract] ABSTRACT: Cyclosporin A is a widely used immunosuppressive drug having toxic side effects, in particular on kidneys and liver, as a result of its action on different molecular targets. Here we demonstrate that low doses of CsA are able to induce the expression of the heat shock protein HSP27 and its hyperphosphorylation. It also activates the two heat shock transcription factors, HSF1 and HSF2. Since these factors have been shown to be activated by proteasome inhibition, we tested the hypothesis that the inhibitory action of CsA on the proteasome might be responsible for the activation of HSFs and the subsequent expression of HSP27. The increase in multiubiquitinated proteins as well as the stabilization of p53 following CsA addition argues in favor of this hypothesis. The kidney BSC-1 cells are highly responsive to the addition of CsA: the possible link between HSP27 induction and hyperphosphorylation and nephrotoxicity is discussed.
Biochemical and Biophysical Research Communications 04/2000; 269(2):464-9.
[show abstract][hide abstract] ABSTRACT: Until recently, little attention has been devoted to palaeoclimate records in western Central Asia although the potential for improving our understanding of the connections between local and regional climate changes in this region is high. The location of the Aral Sea in the heart of western Central Asia offers a unique opportunity to scrutinise palaeoenvironmental changes during the Holocene, and particularly over the last few thousand years, in a region that is dominated by a continental climate regime and is relatively isolated from the monsoons to the south and southeast. Aral Sea sediments provide an excellent opportunity for high-resolution studies of past climatic and hydrological changes in the catchment area. We review recent palaeoenvironmental work in the region and focus on recent investigations on core material from the Aral Sea that details marked ‘sea level’ oscillations over the past ca. 2000 years as the Aral responded to local climate forcing. Furthermore, archaeological and digital terrain modelling reveal that the previously proposed mid-Holocene highstand of the Aral Sea at 72–73 m a.s.l. cannot have been achieved, a revised Holocene highstand is set at about 54–55 m a.s.l.