diamide and 6-hydroxy-2-5-7-8-tetramethylchroman-2-carboxylic-acid

Cellular thiol groups modulate various aspects of cellular function, including cell death. In this study, we found that a thiol oxidant, diamide, induced morphological changes such as cell swelling, membrane blebbing, and chromatin condensation in Aplysia cultured sensory neurons. Furthermore, diamide induced biphasic changes in the membrane potential, where hyperpolarization was followed by depolarization. Moreover, these diamide-induced cytotoxic effects were completely blocked by the equimolar addition of the disulfide reducing agent dithiothreitol (DTT). We also found that during H(2)O(2)-induced cell death, DTT attenuated cell swelling and membrane blebbing, but not DNA breakage, whereas the vitamin E analogue trolox attenuated DNA breakage, but not cell swelling and membrane blebbing. These results demonstrate that during H(2)O(2)-induced cell death, apoptotic features such as DNA breakage are mediated in part by free radical generation, whereas necrotic features such as cell swelling and membrane blebbing are primarily mediated by the oxidation of cellular thiol groups.

Topics: Animals; Antioxidants; Aplysia; Cell Death; Cells, Cultured; Chromans; Diamide; Dithiothreitol; Dose-Response Relationship, Drug; Drug Interactions; Electrophysiology; Hydrogen Peroxide; In Situ Nick-End Labeling; Membrane Potentials; Models, Biological; Neurons, Afferent; Oxidants; Potassium Channel Blockers; Propidium; Sulfhydryl Reagents; Tetraethylammonium; Time Factors