Calbindin-D28k buffers intracellular calcium and promotes resistance to degeneration in PC12 cells.
The calcium-binding protein calbindin-D28k (CB) has been hypothesized to function, in part, as a neuroprotective protein. CB is localized within nerve cells that are often less vulnerable to degeneration in patients with Alzheimer's disease and Parkinson's disease, and cells containing 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 cells, transfected to express different levels of CB, were found to be significantly less vulnerable to degeneration caused by serum withdrawal, glutamate, and the neurotoxin 1-methyl-4-phenylpyridinium (MPP+). However, CB did not protect cells from degeneration caused by the calcium ionophore A23187. CB-transfected cells exhibited reduced elevations in [Ca2+]i following treatment with bradykinin, or ATP compared to non-CB-containing cells. These data indicate that CB can protect cells from degeneration caused by certain conditions, and it reduces elevations in [Ca2+]i caused by influx from extracellular sources.
McMahon
A
A
Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas 75235-9070, USA.
Wong
B S
BS
Iacopino
A M
AM
Ng
M C
MC
Chi
S
S
German
D C
DC
D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D064092:Calbindin 1; D064026:Calbindins; D000001:Calcimycin / Q000633:toxicity; D002118:Calcium / Q000378:metabolism*; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D018698:Glutamic Acid / Q000633:toxicity; D007424:Intracellular Fluid / Q000378:metabolism*; D009410:Nerve Degeneration / Q000473:pathology*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D016716:PC12 Cells; D051381:Rats; D064030:S100 Calcium Binding Protein G / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D013997:Time Factors
C576500:Calb1 protein, rat; D064092:Calbindin 1; D064026:Calbindins; D016895:Culture Media, Serum-Free; D009419:Nerve Tissue Proteins; D064030:S100 Calcium Binding Protein G; D000001:Calcimycin; D018698:Glutamic Acid; D015655:1-Methyl-4-phenylpyridinium; D002118:Calcium