10.1046/j.1471-4159.2000.0751878.x
Crossref journal-article
Wiley
Journal of Neurochemistry (311)
Abstract

Abstract: The membrane‐permeant oxidizing agent 2,2′‐dithiodipyridine (DTDP) can induce Zn2+ release from metalloproteins in cell‐free systems. Here, we report that brief exposure to DTDP triggers apoptotic cell death in cultured neurons, detected by the presence of both DNA laddering and asymmetric chromatin formation. Neuronal death was blocked by increased extracellular potassium levels, by tetraethylammonium, and by the broad‐spectrum cysteine protease inhibitor butoxy‐carbonyl‐aspartate‐fluoromethylketone. N,N,N′,N′‐Tetrakis‐(2‐pyridylmethyl)ethylenediamine (TPEN) and other cell‐permeant metal chelators also effectively blocked DTDP‐induced toxicity in neurons. Cell death, however, was not abolished by the NMDA receptor blocker MK‐801, by the intracellular calcium release antagonist dantrolene, or by high concentrations of ryanodine. DTDP generated increases in fluorescence signals in cultured neurons loaded with the zinc‐selective dye Newport Green. The fluorescence signals following DTDP treatment also increased in fura‐2‐ and magfura‐2‐loaded neurons. These responses were completely reversed by TPEN, consistent with a DTDP‐mediated increase in intracellular free Zn2+ concentrations. Our studies suggest that under conditions of oxidative stress, Zn2+ released from intracellular stores may contribute to the initiation of neuronal apoptosis.

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Aizenman, E., Stout, A. K., Hartnett, K. A., Dineley, K. E., McLaughlin, B., & Reynolds, I. J. (2000). Induction of Neuronal Apoptosis by Thiol Oxidation. Journal of Neurochemistry, 75(5), 1878–1888. Portico.

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Dates
Type When
Created 22 years, 5 months ago (March 12, 2003, 1:48 a.m.)
Deposited 1 year, 10 months ago (Oct. 29, 2023, 10:18 a.m.)
Indexed 2 months ago (July 1, 2025, 3:14 p.m.)
Issued 24 years, 10 months ago (Nov. 1, 2000)
Published 24 years, 10 months ago (Nov. 1, 2000)
Published Online 23 years, 8 months ago (Jan. 4, 2002)
Published Print 24 years, 10 months ago (Nov. 1, 2000)
Funders 0

None

@article{Aizenman_2000, title={Induction of Neuronal Apoptosis by Thiol Oxidation: Putative Role of Intracellular Zinc Release}, volume={75}, ISSN={1471-4159}, url={http://dx.doi.org/10.1046/j.1471-4159.2000.0751878.x}, DOI={10.1046/j.1471-4159.2000.0751878.x}, number={5}, journal={Journal of Neurochemistry}, publisher={Wiley}, author={Aizenman, Elias and Stout, Amy K. and Hartnett, Karen A. and Dineley, Kirk E. and McLaughlin, BethAnn and Reynolds, Ian J.}, year={2000}, month=nov, pages={1878–1888} }