INDUCTION OF METALLOTHIONEIN IN MOUSE-LIVER BY VALPROIC ACID

Intraperitoneal injection of valproic acid (VPA) induces metallothionein (MT) in mouse liver. There was a clear-cut dose-dependency and the maximal amount of MT induced by VPA was about 6 times the basal level. The hepatic MT level reached the peak value at 24 h after VPA injection. Neither Cu nor Zn concentrations showed any significant changes after VPA administration in either the whole liver, or in the mitochondrial or supernatant fractions of the liver homogenate. Gel filtration profiles for the supernatant of the liver homogenate of the VPA-treated mice, however, clearly showed that induced MT was chiefly Zn-thionein. Therefore, Zn molecules necessary for the elevated MT levels seem to originate mainly from cytosolic Zn-containing proteins except for MT.