INCREASE OF ADENYLATE KINASE ISOZYME-1 PROTEIN DURING NEURONAL DIFFERENTIATION IN MOUSE EMBRYONAL CARCINOMA P19 CELLS AND IN RAT-BRAIN PRIMARY CULTURED-CELLS

Adenylate kinase (AK), which catalyzes the equilibrium reaction among AMP, ADP, and ATP, is considered to participate in the homeostasis of energy metabolism in cells. Among three vertebrate isozymes, AK isozym e 1 (AK1) is present prominently in the cytosol of skeletal muscle and brain. When mouse embryonal carcinoma P19 cells were differentiated b y retinoic acid into neural cells, the amount of AK1 protein and enzym e activity increased about fivefold concomitantly with neurofilament ( NF). Double-immunofluorescence staining showed that both AK1 and NF we re located in neuronal processes as well as the perinuclear regions in neuronlike cells, but not in glia-like cells. The amount of brain-typ e creatine kinase increased only twofold during P19 differentiation. T he AK isozyme 2, which was not detected in adult mouse brain, was foun d in P19 cells and did not increase during the differentiation. Mitoch ondrial AK isozyme 3, which uses GTP instead of ATP as a phosphate don or, was increased significantly. Immunohistochemical analysis with the primary cultured cells from rat cerebral cortex showed similar cellul ar localization of AK1 to those observed with differentiated P19 cells . These results suggest an important role of this enzyme in neuronal f unctions and in neuronal differentiation.