Calcium and Fos Involvement in Brain‐Derived Ca²⁺‐Binding Protein (S100)‐Dependent Apoptosis in Rat Phaeochromocytoma Cells

Abstract

Brain‐derived calcium‐binding protein S100 induces apoptosis in a significant fraction of rat phaeochromocytoma (PC12) cells. We used single cell techniques (patch clamp, videomicroscopy and immunocytochemistry) to clarify some of the specific aspects of S100‐induced apoptosis, the modality(ies) of early intracellular Ca2+ concentration increase and the expression of some classes of genes (c‐fos, c‐jun, bax, bcl‐x, p‐15, p‐21) known to be implicated in apoptosis of different cells. The results show that S100: (1) causes an increase of [Ca2+]i due to an increased conductance of L‐type Ca2+ channels; (2) induces a sustained increase of the Fos levels which is evident since the first time point tested (3 h) and remains elevated until to the last time point (72 h). All these data suggest that S100‐derived apoptosis in PC12 cells may be the consequence of a system involving an increase in L‐type Ca2+ channel conductance with consequent [Ca2+]i increase which up‐regulates, directly or indirectly, the expression of Fos.

Increased susceptibility of S100B transgenic mice to perinatal hypoxia‐ischemia

“…Cytokine‐stimulated glia can kill neurons via an NO‐dependent mechanism,18, 21, 22 suggesting that S100B induction of proinflammatory cytokines may directly, or in concert with other glial stimulators, promote an increase in NO‐mediated neuronal death. S100B also has been reported to exert direct neurotoxic effects23 or induce apoptotic neuronal death through interaction with the receptor for advanced glycation end products 24. These data suggest that S100B is neurotoxic in sufficiently high concentrations in the vicinity of susceptible neurons.…”

Serum S100β Protein in Children With Acute Recurrent Headache: A Potentially Useful Marker for Migraine

“…NO may be pivotal to the initiation and maintenance of migraine headache 21 . Also, S100β has been reported to exert direct neurotoxic effects 22 or induce apoptotic neuronal death through interaction with the receptor for advanced glycation end products 23 . These data suggest that S100β at sufficiently high concentrations is neurotoxic for susceptible neurons.…”

S100A1: Structure, Function, and Therapeutic Potential

“…There is reason to believe such inhibition studies could prove to be medicinally relevant; neuronal PC12 cells that do not express S100A1 are more resistant to A -induced cell death than cells that express normal levels of S100A1 [3], indicating that S100A1 antagonists could have potential for treating Alzheimer's disease. In addition, extracellular S100A1 is cytotoxic to PC12 cells (Zimmer, unpublished observations; [58,59]) and injection of anti-S100A1 antibodies was found to lessen learning and memory deficits [60]. Other S100A1-regulated intracellular processes are also consistent with S100A1 augmentation of Alzheimer's disease pathology including S100A1-linked altered amyloid precursor protein expression, destabilization of calcium homeostasis, S100A1-mediated increased cell growth, decreased dendritic arborization, and decreased tubulin polymerization/stability [3,61].…”