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A genome-wide association study suggested that a R504H mutation in the proprotein convertase PC7 is associated with increased circulating levels of HDL and reduced triglycerides in black Africans. Our present results show that PC7 and PC7-R504H exhibit similar processing of transferrin receptor-1, proSortilin, and apolipoprotein-F. Plasma analyses revealed no change in the lipid profiles, insulin or glucose of wild type and PC7 KO mice. Thus, the R504H mutation does not modify the proteolytic activity of PC7. The mechanisms behind the implication of PC7 in the regulation of human HDL, triglycerides and in modifying the levels of atherogenic small dense LDL remain to be elucidated.

The amyloid peptide (Abeta) of Alzheimer's disease (AD) is produced by proteolytic cleavage of a larger precursor, the amyloid peptide precursor or APP. The discovery of pathogenic mutations in the APP gene provides strong evidence for the hypothesis that APP metabolism is involved in the etiology of AD. To study the metabolism of the protein, human APP has been expressed in several mammalian cell types. Insect cells, infected by a recombinant baculovirus carrying the human APP sequence, also provide an interesting expression system because these cells do not produce endogenous APP. Baculovirus-infected cells synthesize very high amounts of extracellular soluble APP, after cleavage of the transmembrane protein, as described for mammalian cells. However, we demonstrate here that insect cells do not produce Abeta from APP. These results suggest that while the enzymatic activity needed for the production of soluble APP is conserved between insect and mammalian cells, the enzymes required for the production of Abeta from APP are only expressed in mammalian cells.