Increased expression of prion protein is associated with changes in dopamine metabolism and MAO activity in PC12 cells

Prion diseases of humans and animals occur following infection with infecti ous agents containing PrPSc or in situations in which there is a mutation o f the prion protein (PrP) gene. The cellular prion protein (PrPC) is a sial oglycoprotein that is expressed predominantly in neurons. PrPC is converted into a pathogenic form of PrP (PrPSc), which is distinguishable from PrPC by its relative resistance to protease digestion. A number of postulates ha ve been advanced for the function of normal PrP (PrPC), but this issue has not been resolved. To investigate the function(s) of PrPC, we established c lonal PC12 cell lines, which have elevated PrPC expression. The results sho w that there were alterations in dopamine metabolism and in monoamine oxida se (MAO) activity in transfected PC12 cells that overexpress PrPC. There wa s an increase in concentration of DOPAC, a metabolite of dopamine, and in M AO activity in cells overexpressing PrPC. MAO is involved in oxidative degr adation of dopamine (DA). Our data suggest that PrPC plays a role in DA met abolism by regulating MAO activity.