Uncoupling protein 2 negatively regulates neurite extensions in PC12h cells

Uncoupling protein 2 (UCP2) distributes in many organs including the brain. Though recent reports suggest that UCP2 is involved in the neuroprotection and the regulation of neurosecretion, the roles of UCP2 in the central nervous systems remain largely unclear. In order to clarify the significance of UCP2 in the brain especially at developmental stage, subcellular localizations of rat UCP2 (rUCP2) in the developing cerebellar Purkinje cells were immunochemically examined. The rUCP2-like immunoreactivities observed axon or its terminal during axonal maturation. This result implies that rUCP2 contributes to the neurite development. In the PC12h cells overexpressing rUCP2 or active mutant of rUCP2, the neurite outgrowth was significantly inhibited along with a reduction of cellular ATP level. These findings suggest a possibility that UCP2 is involved in negative regulation of neurite extensions through repression of the energy supply.