Parat M O, Richard M J, Favier A, Béani J C
Groupe de Recherche sur les Pathologies Oxydatives, CHU Albert Michallon, Grenoble, France.
Biol Trace Elem Res. 1998 Dec;65(3):261-70. doi: 10.1007/BF02789101.
Heat shock protein (HSP) synthesis results from various types of injury, including heat shock (HS) and some oxidants. The intracellular signals leading to HSP synthesis are not yet fully elucidated. We have studied the influence of NNN'N'-tetrakis(2-pyridylmethyl)ethylene diamine (TPEN), a metal chelator known to induce cellular zinc and copper deprivation, on resistance to heat and on hsp70 synthesis in HaCaT keratinocytes. TPEN was shown to sensitize HaCaT cells to heat shock. The effect of TPEN was neutralized by equimolar Zn2+. By the use of sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis and Western blotting characterization of hsp70, it was shown that cultured HaCaT cells constitutively express the inducible form of hsp70. The application of TPEN alone slightly increases the level of hsp70 but inhibits its induction by HS. This inhibitory effect is related to metal deprivation, because it is eliminated when Cu2+ or Zn2+ ions are supplied together with TPEN. These results suggest that these metals are involved in the expression by keratinocytes of a stress protein which has a protective action against environmental stress.
热休克蛋白（HSP）的合成源于各种类型的损伤，包括热休克（HS）和某些氧化剂。导致HSP合成的细胞内信号尚未完全阐明。我们研究了NNN'N'-四（2-吡啶甲基）乙二胺（TPEN），一种已知可诱导细胞锌和铜缺乏的金属螯合剂，对HaCaT角质形成细胞耐热性和hsp70合成的影响。结果表明，TPEN可使HaCaT细胞对热休克敏感。等摩尔的Zn2+可中和TPEN的作用。通过十二烷基硫酸钠-聚丙烯酰胺凝胶电泳分析和hsp70的蛋白质印迹表征，表明培养的HaCaT细胞组成性表达可诱导形式的hsp70。单独应用TPEN会轻微增加hsp70的水平，但会抑制HS对其的诱导。这种抑制作用与金属缺乏有关，因为当Cu2+或Zn2+离子与TPEN一起提供时，这种抑制作用就会消除。这些结果表明，这些金属参与角质形成细胞中一种应激蛋白的表达，该应激蛋白对环境应激具有保护作用。
