factor is regulated by protein kinase A Abnormal expression of serum amyloid A (SAA), a family of proteins,is linked with several chronic inflammatory diseases including secondary amyloidosis, rheumatoid arthritis and atherosclerosis. Thus, it is important to understand the induction mechanism of SAA expression. SAA activating factor (SAF) has recently been identified as one of the major transcription factors that control SAA gene expression under inflammatory condition. Activation of SAF by many inflammatory agents including interleukins 1 and 6, bacterial lipopolysaccharide, and oxidized low density lipoprotein triggers its increased binding to a proximal promoter element of rabbit SAA2 gene and transcriptional induction of the target gene. Further studies have indicated that a phosphorylation event involving serinekhreonine protein kinase(s) is a key step in the activation of SAF. In the present report, we show that protein kinase A (PKA)is at least partly responsible for the phosphorylation of SAF. Phosphorylation of SAF by PKA increases its DNA-binding ability. Co-transfection analysis has indicated that transactivation potential of SAF is increased by PKA possibly due to increased D N A binding of the phosphorylated SAF. Phosphorylation of SAF is also necessary for its translocation from cytoplasm to nucleous and PKA plays an important role in this process. These findings form the basis of a signalling pathway that leads to activation of SAF for increased expression of SAA under inflammatory condition. (Supported by USPHS Grant DK49205 and funds from the College of Veterinary Medicine, University of Missouri) 797 CD36 scavenger receptor expression and oxLDL uptake R. Ricciarelli. 1.M. Z ingg and A. Azzi Biihlstrasse, 28 3012 Bern Switzerland are inhibited by vitamin E Vitamin E is well known as an antioxidant and numerous studies suggest that it has a preventive role in atherosclerosis,although the mechanism of action still remains unclear. The original aim of this study was to establish whether alphatocopherol (the most active form of vitamin E) acts at the earliest events on the cascade of atherosclerosis progression, the one of oxidized LDL (oxLDL) uptake and foam cell formation. We show here that the CD36 scavenger receptor (a specific receptor for oxLDL) is expressed in human aortic smooth muscle cells (SMC). Treatment of SMC and macrophages with alpha-tocopherol, downregulates CD36 expression by reducing its promoter activity. Furthermore, we find that alphatocopherol treatment of SMC leads to a reduction of oxLDL uptake. This study indicates for the first time that CD36 is expressed in human SMC. In these cells CD36 transports oxLDL into the cytosol, as monitored by confocal microscopy.In conclusion, alpha-tocopherol inhibits oxLDL uptake, by a mechanism involving downregulation of CD36 mRNA and protein expression. Therefore, the beneficial effects of alphatocopherol against atherosclerosis can be, at least in part, explained by its effect of lowering the uptake of oxidized lipoproteins, with consequ...
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