Induction of apoptosis in Neuro-2A cells by Zn2+ chelating.
Metal ions such as Ca2+, Mg2+, or Zn2+, are important for many cell functions, for example, signal transduction and the modulation of enzyme activity. The relationship between apoptosis and metal cations, especially Ca2+, has been described in many reports. We have investigated the role of metal cations in the regulation of apoptosis in the mouse neuroblastoma cell line, Neuro-2A. When Neuro-2A cells were treated with ethylene diaminetetraacetic acid (EDTA), apoptosis was detected as growth inhibition, DNA fragmentation with a ladder pattern in agarose gel electrophoresis, and nuclear decomposition. However, in case of the treatment with ethylene glycol bis- (beta-aminoethyl ether) N,N,N',N'-tetraacetic acid (EGTA), which has a higher chelating specificity for Ca2+ than EDTA, DNA fragmentation was not detected. Moreover, the apoptosis induced by EDTA was inhibited by exogenous Zn2+. The membrane permeable Zn2+ chelator N,N,N',N'-tetrakis (2-pyridylmethyl)ethylenediamine (TPEN) also induced apoptosis of the Neuro-2A cells, and addition of equimolar exogenous Zn2+ or Cu2+, but not Mn2+ or Fe2+, prevented TPEN-induced apoptosis. The results suggest that Zn2+ may be a key regulator of apoptosis in Neuro-2A cells.
Sakabe
I
I
Department of Biological and Chemical Engineering, Faculty of Engineering, Gunma University, Japan.
Paul
S
S
Dansithong
W
W
Shinozawa
T
T
D000818:Animals; D017209:Apoptosis; D002455:Cell Division / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects / Q000473:pathology; D002614:Chelating Agents / Q000494:pharmacology*; D003300:Copper / Q000494:pharmacology; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004492:Edetic Acid / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D005029:Ethylenediamines / Q000494:pharmacology; D007501:Iron / Q000494:pharmacology; D008345:Manganese / Q000494:pharmacology; D051379:Mice; D009447:Neuroblastoma / Q000473:pathology*; D014407:Tumor Cells, Cultured; D015032:Zinc / Q000494:pharmacology / Q000502:physiology*
D002614:Chelating Agents; D005029:Ethylenediamines; D008345:Manganese; D004533:Egtazic Acid; D003300:Copper; D004492:Edetic Acid; D007501:Iron; D015032:Zinc; C044387:N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine