calcimycin and Calcium-Metabolism-Disorders

Disruption of intracellular calcium homeostasis is thought to play a role in neurodegenerative disorders such as Huntington's disease (HD). To study different aspects of putative pathogenic mechanisms in HD, we aimed to establish an in vitro model of calcium-induced toxicity in striatal neurons. The calcium ionophore A23187 induced a concentration- and time-dependent cell death in cultures of embryonic striatal neurons, causing both apoptosis and necrosis. Cell death was significantly reduced by the cell-permeant antioxidant manganese(III)tetrakis(4-benzoic acid) porphyrin (MnTBAP). Cyclosporin A and its analogue N-MeVal-4-cyclosporin also reduced the incidence of cell death, suggesting the participation of mitochondrial permeability transition in this process. Furthermore, addition of either of two types of caspase inhibitors, Ac-YVAD-CHO (acetyl-Tyr-Val-Ala-Asp-aldehyde) and Ac-DEVD-CHO (acetyl-Asp-Glu-Val-Asp-aldehyde), to the striatal cells blocked A23187-induced striatal cell death in a concentration-dependent manner. These results suggest that oxidative stress, opening of the mitochondrial permeability transition pore and activation of caspases are important steps in A23187-induced cell death.

Topics: Animals; Calcimycin; Calcium; Calcium Metabolism Disorders; Caspases; Cell Culture Techniques; Cell Death; Cell Membrane Permeability; Corpus Striatum; Cyclosporine; Cysteine Proteinase Inhibitors; Embryo, Mammalian; Enzyme Inhibitors; Free Radical Scavengers; Ionophores; Metalloporphyrins; Mitochondrial Swelling; Neurons; Oligopeptides; Oxidative Stress; Rats; Rats, Sprague-Dawley; Time Factors

Topics: Arachidonic Acids; Blood Platelet Disorders; Blood Platelets; Calcimycin; Calcium Metabolism Disorders; Child, Preschool; Female; Humans; Male; Middle Aged; Platelet Aggregation