This paper provides further characterization of a receptor that, in cells lacking the LDL receptor (FH fibroblasts), mediates lipoprotein binding, uptake, and degradation when incubated with oleate at concentrations not exceeding albumin binding capacity. This oleate-activated receptor is genetically distinct from the LDL receptor and is hereafter referred to as the lipolysis-stimulated receptor (LSR). Its apparent affinity was higher for triglyceride-rich lipoproteins (chylomicrons, VLDL) and for lipid emulsions supplemented with recombinant apoE, than for LDL which contains solely apoB. In contrast, VLDL isolated from a Type III hyperlipidemic patient (apoE2/2 phenotype) failed to bind to the LSR. Five lines of evidence indicated that the LSR is distinct from the LDL receptor-related protein (LRP): (1) the LRP ligand, alpha 2-macroglobulin-methylamine (alpha 2-MG*), did not bind to the oleate-induced LDL binding site; (2) oleate had no effect on the binding of alpha 2-MG* to LRP; (3) the LRP-associated protein, RAP, which inhibits LRP, had no effect on the LSR; (4) binding of lipoproteins to LSR was independent of Ca2+; and (5) LSR activity resolved as two proteins smaller than LRP (apparent molecular masses as determined by ligand blots: 115 and 85 kDa). That LSR provides a new candidate receptor contributing to the clearance of chylomicron remnants (CMR) is supported by the observation that LSR was inhibited by lactoferrin, a milk protein that delays CMR clearance when injected in vivo. Furthermore, in primary cultures of rat hepatocytes, oleate stimulated binding, uptake, and degradation of LDL with kinetic characteristics similar to that of LSR expressed in FH fibroblasts.(ABSTRACT TRUNCATED AT 250 WORDS)

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The earliest second messenger discovered was the CAMP. cAMP weakly penetrates into the cell. O n the other hand, dibutyryl cAMP is membrane-penetratible derivative of the CAMP, which shows high activity and at present time is largerly used in experiments.The comparative study of the effects of cAMP and dibutyryl cAMP on the structure of monoolein-water cubic liquid-crystalline phase have been performed by X-ray diffraction, Raman, and FTIR spectroscopies. Based on the X-ray diffraction data it was established that cAMP does not change the structure of Pn3m lattice, contrary to dibutyryl cAMP which induces transformation from Pn3m to Ia3d lattice. The H-bonding interaction between the anionic phosphate group of cAMP and the glycerol backbone of the lipids has been evidenced by the increased frequency of the symmetric stretching vibration of PO2 group by 4-6 cm-l and broadening by 7 cm-l of the stretching vibration of glycerol C-OH group. It was found that dibutyryl cAMP interacts with the cubic phase through the pyrimidine ring and contrary to cAMP shows tendency to increase the number of gauche defects and to lower the mobility of the acyl chains.= 970 Proteasomes regulate the duration of erythropoietin receptor activation by controlling down-regulation of cell surface receptors