NO donor and ONOO- donor regulated expression of porphyrin transporter

We reported that the nitric oxygen (NO) inactivation of a catalytic enzyme ferrochelatase increased by intracellular porphyrin accumulation: the ferrochelatase chelates iron into protoporphyrin to form protoheme. Since high NO concentration of cell is cancer specific phenomenon, the cellular porphyrin accumulation is a cancer specific event. Not only the porphyrin biosynthesis, but NO may also regulate porphyrin transports. Reactive nitrogen species such as NO or peroxynitrite (ONOO-) have physiological activity. ONOO- is generated by a fast reaction between NO and superoxide anion. Thus it is not well known that which compounds are important to accumulation of porphyrin. In this study, we investigated whether expression of porphyrin transporter is effected by NO donor (NOC18) or ONOO- donor (SIN1). Expression of heme carrier protein 1 (HCP-1), is known of porphyrin transporter, was determined by Western blot analysis and it was up-regulated by treatment with NOC18 or SIN1. In order to investigate cellular uptake manner of hematopophyrin derivatives (HpD) in association with NO donor or ONOO- donor, cellular uptake of HpD was examined by measuring fluorescent intensities of HpD after exposing it to cells. From these results, both NO donor and ONOO- donor regulated expression of porphyrin transporter and accumulation of porphyrin.