Zinc and DNA fragmentation in keratinocyte apoptosis: its inhibitory effect in UVB irradiated cells.
Zinc has been shown to have antioxidant properties and to exhibit inhibitory effects on apoptosis. In this work we investigated the effect of zinc on DNA integrity and on apoptosis of HaCaT keratinocytes. Cells were submitted to zinc deprivation by a diffusible zinc chelator, (N,N,N',N'-tetrakis (2-pyridylmethyl)ethylenediamine) (TPEN) or supplied with zinc chloride and submitted to UVB radiation. After cell exposure to TPEN for 2 h, strand breaks significantly impaired DNA resistance to alkaline denaturation. DNA strand breaks induced by a 6 h TPEN application were significantly prevented if zinc chloride was supplied together with the chelator. TPEN also generated, after 4-6 h of application, cytoplasmic histone-associated DNA fragments (mononucleosomes and oligonucleosomes), features of cell death by apoptosis. Moreover, UVB irradiation led to early DNA strand breaks and to an increase in cytoplasmic nucleosomes which was maximum 10 h after irradiation. These effects were prevented by the supply of zinc chloride (0.1 mM) in the culture medium. These results suggest that zinc ions interfere with the apoptosis process at an early stage, by decreasing DNA damage able to trigger apoptosis.
Parat
M O
MO
Laboratoire de Biochimie C, CHU Albert Michallon, Grenoble, France.
Richard
M J
MJ
Pollet
S
S
Hadjur
C
C
Favier
A
A
Béani
J C
JC
D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D002614:Chelating Agents / Q000494:pharmacology; D053938:DNA Fragmentation / Q000528:radiation effects; D005029:Ethylenediamines / Q000494:pharmacology; D006801:Humans; D015603:Keratinocytes / Q000166:cytology*; D014466:Ultraviolet Rays; D015032:Zinc / Q000502:physiology*
D002614:Chelating Agents; D005029:Ethylenediamines; D015032:Zinc; C044387:N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine