Regulation of thioredoxin reductase by calcium in Hermansky-Pudlak syndrome.

Cell cultures of keratinocytes, established from four Hermansky-Pudlak syndrome (HPS) homozygotes yielded low membrane-associated thioredoxin reductase activities compared with normal healthy adult controls. This low activity has been shown to be caused by a special sensitivity of the enzyme to calcium. 45Calcium has been used to compare the kinetics for the transport and bioaccumulation of this regulatory cation in keratinocyte cultures of a kindred with HPS (i.e., one HPS homozygote, one HPS obligate heterozygote, one normal family member, and healthy adult controls). The results show that both HPS-homozygous and -heterozygous cells bind more extracellular calcium than noncarriers of this genetic defect, and HPS homozygous cells appear to have a defective calcium transport system.