Expression of metallothionein-III and cell death in differentiated catecholaminergic neuronal cells

Metallothionein (MT)-III, an isomer of metallothionein, is also known to be a growth inhibitory factor. MT-III has been reported to decrease the number of surviving neuronal cells in culture medium containing brain extract. Using differentiated catecholaminergic neuronal CATH.a cells treated with dibutyryl cyclic AMP, we examined MT-III expression and the effect of mouse forebrain extract on cell viability. Increase in MT-III expression was revealed in the differentiated cells. Moreover, treatment with mouse forebrain extract induced apoptotic cell death in differentiated CATH.a cells, accompanied by decreases in both MT-III and a neuronal differentiation marker, growth-associated protein-43, expression in surviving cells. These results imply that MT-III expression during the developmental period may be associated with the regulation of normal neural differentiation.