V-1, a Positive Regulator of Tyrosine Hydroxylase Gene Expression, Promotes Maitotoxin- and Palytoxin-induced Norepinephrine Secretion in PC12D Cells

摘要

V-1 is an ankyrin repeat protein which binds to CapZ, an actin capping protein, thereby inhibiting CapZ to modulate actin dynamics. V-1 also serves as a positive regulator of TH gene expression and catecholamine (CA) biosynthesis in cultured cells. Moreover, V-1 stimulates high K~+induced dopamine secretion in PC12D cells. In the present study, we more precisely examined the functional significance of V-1 in CA secretion in PC1 2D cells by using two pharmacological tools with the activity to trigger Ca~(2+)-influx, i.e. maitotoxin (MTX), a marine toxin activating Ca~(2+) channels, and palytoxin (PTX), another capable of activating Na~+-dependent and tetrodotoxin-insensitive voltage-dependent Ca~(2+) channels. Both toxins increased norepinephrine (NE) secretion in PCI 2D cells. In PCI 2D cells which stably overexpress V-1, MTX- and PTX-induced NE secretion was more remarkably stimulated than in a mock cell line. These findings suggest that V-1 could regulate Ca~(2+)-influx-dependent NE secretion possibly by modulation of actin dynamics in the adrenal chromaffin cells.