These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: The thiol-modifying agent N-ethylmaleimide elevates the cytosolic concentration of free Zn(2+) but not of Ca(2+) in murine cortical neurons.
    Author: Gibon J, Tu P, Frazzini V, Sensi SL, Bouron A.
    Journal: Cell Calcium; 2010 Jul; 48(1):37-43. PubMed ID: 20667413.
    Abstract:
    The membrane permeant alkylating agent N-ethylmaleimide (NEM) regulates numerous biological processes by reacting with thiol groups. Among other actions, NEM influences the cytosolic concentration of free Ca(2+) ([Ca(2+)]i). Depending on the cell type and the concentration used, NEM can promote the release of Ca(2+), affect its extrusion, stimulate or block its entry. However, most of these findings were obtained in experiments that employed fluorescent Ca(2+) probes and one major disadvantage of such experimental setting derives from the lack of specificity of the probes as all the so-called "Ca(2+)-sensitive" indicators also bind metals like Zn(2+) or Mn(2+) with higher affinities than Ca(2+). In this study, we examined the effects of NEM on the [Ca(2+)]i homeostasis of murine cortical neurons. We performed live-cell Ca(2+) and Zn(2+) imaging experiments using the fluorescent probes Fluo-4, FluoZin-3 and RhodZin-3 and found that NEM does not affect the neuronal [Ca(2+)]i homeostasis but specifically increases the cytosolic and mitochondrial concentration of free Zn(2+)([Zn(2+)]i). In addition, NEM triggers some neuronal loss that is prevented by anti-oxidants such as N-acetylcysteine or glutathione. NEM-induced toxicity is dependent on changes in [Zn(2+)]i levels as chelation of the cation with the cell-permeable heavy metal chelator, N,N,N'N'-tetrakis(-)[2-pyridylmethyl]-ethylenediamine (TPEN), promotes neuroprotection of cortical neurons exposed to NEM. Our data indicate that NEM affects [Zn(2+)]i but not [Ca(2+)]i homeostasis and shed new light on the physiological actions of this alkylating agent on central nervous system neurons.
    [Abstract] [Full Text] [Related] [New Search]