Thiol oxidation-mediated cell death in Aplysia cultured sensory neurons.
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.
Chang
Deok-Jin
DJ
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.
Lee
Seung-Hee
SH
Lim
Chae-Seok
CS
Jang
Dong-Hyuk
DH
Lee
Chi-Hoon
CH
Lee
Young-Don
YD
Kaang
Bong-Kiun
BK
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
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