Parat M O, Richard M J, Pollet S, Hadjur C, Favier A, Béani J C
Laboratoire de Biochimie C, CHU Albert Michallon, Grenoble, France.
J Photochem Photobiol B. 1997 Jan;37(1-2):101-6. doi: 10.1016/s1011-1344(96)07334-4.
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.
锌已被证明具有抗氧化特性，并对细胞凋亡表现出抑制作用。在这项工作中，我们研究了锌对HaCaT角质形成细胞DNA完整性和细胞凋亡的影响。通过一种可扩散的锌螯合剂（N,N,N',N'-四（2-吡啶甲基）乙二胺）（TPEN）使细胞处于锌缺乏状态，或给细胞提供氯化锌并使其接受UVB辐射。细胞暴露于TPEN 2小时后，链断裂显著损害了DNA对碱性变性的抗性。如果在加入螯合剂的同时提供氯化锌，则可显著防止由TPEN作用6小时诱导的DNA链断裂。在应用TPEN 4 - 6小时后，还产生了细胞质中与组蛋白相关的DNA片段（单核小体和寡核小体），这是细胞凋亡导致细胞死亡的特征。此外，UVB照射导致早期DNA链断裂，并使细胞质核小体增加，在照射后10小时达到最大值。在培养基中提供氯化锌（0.1 mM）可防止这些效应。这些结果表明，锌离子通过减少能够触发细胞凋亡的DNA损伤，在早期干扰细胞凋亡过程。
