title: Thiol oxidation-mediated cell death in Aplysia cultured sensory neurons.
abstract: 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.
authors.affiliation: National Research Laboratory, Institute of Molecular Biology and Genetics, School of Biological Sciences, College of Natural Sciences, Seoul National University, San 56-1 Silim-dong Kwanak-gu, Seoul 151-742, South Korea.
authors.forename: Deok-Jin
authors.initials: DJ
authors.lastname: Chang
authors.forename: Seung-Hee
authors.initials: SH
authors.lastname: Lee
authors.forename: Chae-Seok
authors.initials: CS
authors.lastname: Lim
authors.forename: Dong-Hyuk
authors.initials: DH
authors.lastname: Jang
authors.forename: Chi-Hoon
authors.initials: CH
authors.lastname: Lee
authors.forename: Young-Don
authors.initials: YD
authors.lastname: Lee
authors.forename: Bong-Kiun
authors.initials: BK
authors.lastname: Kaang
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001048:Aplysia; D016923:Cell Death; D002478:Cells, Cultured; D002839:Chromans / Q000494:pharmacology; D003958:Diamide / Q000494:pharmacology*; D004229:Dithiothreitol / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004594:Electrophysiology / Q000379:methods; D006861:Hydrogen Peroxide / Q000494:pharmacology; D020287:In Situ Nick-End Labeling / Q000379:methods; D008564:Membrane Potentials / Q000187:drug effects; D008954:Models, Biological; D009475:Neurons, Afferent / Q000166:cytology / Q000187:drug effects*; D016877:Oxidants / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D011419:Propidium / Q000378:metabolism; D013439:Sulfhydryl Reagents / Q000494:pharmacology*; D019789:Tetraethylammonium / Q000494:pharmacology; D013997:Time Factors
chemical_list: D000975:Antioxidants; D002839:Chromans; D016877:Oxidants; D026902:Potassium Channel Blockers; D013439:Sulfhydryl Reagents; D003958:Diamide; D011419:Propidium; D019789:Tetraethylammonium; D006861:Hydrogen Peroxide; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid; D004229:Dithiothreitol