CALBINDIN-D-28K BUFFERS INTRACELLULAR CALCIUM AND PROMOTES RESISTANCETO DEGENERATION IN PC12 CELLS

The calcium-binding protein calbindin-D-28k (CB) has been hypothesized to function, in part, as a neuroprotective protein. CB is localized w ithin nerve cells that are often less vulnerable to degeneration in pa tients with Alzheimer's disease and Parkinson's disease, and cells con taining CB can buffer intracellular calcium concentrations ([Ca2+](i)) . The present study was designed to directly test the hypothesis that CB can protect cells from degeneration by reducing [Ca2+](i). PC12 cel ls, transfected to express different levels of CB, were found to be si gnificantly less vulnerable to degeneration caused by serum withdrawal , glutamate, and the neurotoxin 1-methyl-4-phenylpyridinium (MPP+). Ho wever, CB did not protect cells from degeneration caused by the calciu m ionophore A23187. CB-transfected cells exhibited reduced elevations in [Ca2+](i) following treatment with bradykinin, or ATP compared to n on-CB-containing cells. These data indicate that CB can protect cells from degeneration caused by certain conditions, and it reduces elevati ons in [Ca2+](i) caused by influx from extracellular sources. (C) 1998 Elsevier Science B.V.