No abstract

Multidrug resistance protein 4 (MRP4/ABCC4) has been established as an independent regulator of cyclic AMP (cAMP) levels particularly in vascular smooth muscle cells and in hematopoietic cells. Here, we assessed whether cAMP in turn regulates MRP4. A significant upregulation of MRP4 mRNA and protein by long-term treatment with cAMP-enhancing agents was observed in HeLa cells, smooth muscle cells, and megakaryoblastic leukemia M07e cells. This upregulation was not affected by inhibition of protein kinase A, but could be reverted by inhibitors and siRNA of an alternative cAMP-signaling route involving exchange proteins activated by cyclic AMP (EPAC) and mitogen-activated protein kinases. A selective EPAC activator could equally induce MRP4. The transcriptional regulation was confirmed in a luciferase reporter gene assay using a vector containing a 1494-bp fragment of the promoter region of the MRP4/ABCC4 gene. Our results suggest that enhanced cAMP levels upregulate MRP4 expression, which can result in increased cAMP efflux.

Lubricants for cold forging operations do not only enable a reliable forging process, but also affect the results of forging processes. A sound lubrication decreases the occurring forces and may result in a smooth specimen surface. However, some lubricants are known to increase the initial surface roughness of the specimen as a consequence of the forming. Therefore, the decision which lubricant should be used is of special interest for near-net shape operations. The paper at hand presents the results of a finite element investigation of the first stage of an industrial rod extrusion process which was investigated with two different lubrication systems. The numerical investigations focus on a reliable prediction of the development of the surface roughness in due consideration of the lubricant.

No abstract