Micromolar zinc affects endonucleolytic activity in hydrogen peroxide-mediated apoptosis.
When damaged by hydrogen peroxide, peripheral blood lymphocytes undergo cell death by apoptosis in the absence of internucleosomal DNA cleavage, while, in the same cells, other apoptosis-inducing treatments bring DNA cleavage to completion. However, the formation of internucleosomal DNA fragments is readily obtained if cells are pretreated with a divalent metal chelator, TPEN, at micromolar concentrations. Since the coadministration of equimolar zinc concentrations abrogates the formation of the ladder, a zinc-inhibitable endonucleolytic activity is accounted for the effect. Most notably, subtraction of zinc ions does not increase the percentage of cells undergoing apoptosis, but rather results in a rescue from death.
Marini
M
M
Istituto di Istologia ed Embriologia Generale, University of Bologna, Italy. marinam@alma.unibo.it
Musiani
D
D
D000328:Adult; D017209:Apoptosis / Q000187:drug effects*; D002614:Chelating Agents / Q000494:pharmacology*; D053938:DNA Fragmentation / Q000187:drug effects*; D004706:Endodeoxyribonucleases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005029:Ethylenediamines / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity*; D008214:Lymphocytes / Q000187:drug effects* / Q000648:ultrastructure; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D015032:Zinc / Q000494:pharmacology / Q000502:physiology*
D002614:Chelating Agents; D005029:Ethylenediamines; D016166:Free Radical Scavengers; D006861:Hydrogen Peroxide; D004706:Endodeoxyribonucleases; D015032:Zinc; C044387:N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine