Nerve growth factor inhibits apoptosis induced by S-100 binding in neuronal PC12 cells
Abstract
When grown for seven days in a medium containing nerve growth factor (100 ng/ml), 10% horse serum and 5% fetal bovine serum PC12 cells stopped dividing, extended neurites and assumed a neuronal phenotype. Withdrawal of nerve growth factor from these cells resulted in loss of neurites and apoptotic changes in many cells. The apoptotic changes were exacerbated if the cells were also exposed to 1-2 microM S-100, a calcium binding protein purified from bovine brain. After exposure to S-100, the PC12 cells underwent characteristic apoptotic changes. Within 2 in neurites retracted, the cell body shrunk and submembranous accumulation of condensed cytoplasmic material was observed. DNA ladders were present after 24-48 h and 60% of the cells became hypodiploid after 72 h. S-100 induced apoptosis by binding to specific sites (Kd = 189 nM) on PC12 cells and this caused a rise in [Ca2+]i due to a transmembrane capacitative flux followed by the depletion of internal stores. This increase was reversed if 5 microM nifedipine, a specific L-type Ca2+ channel inhibitor, was added to the medium after S-100 and completely abolished if the cells were pretreated with 5 microM thapsigargin, an inhibitor of endoplasmic reticulum Ca(2+)-ATPase. The pre...Continue Reading
References
Complex I inhibitors induce dose-dependent apoptosis in PC12 cells: relevance to Parkinson's disease
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Apoptosis
Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis