Noda M, Wataha J C, Lewis J B, Lockwood P E, Komatsu H, Sano H
Section of Cariology, Operative Dentistry, and Endodontology, Department of Oral Health Science, Hokkaido University Graduate School of Dental Medicine, Sapporo 060-8586, Japan.
J Biomed Mater Res A. 2003 Oct 1;67(1):240-5. doi: 10.1002/jbm.a.10100.
The biological liabilities that result from the release of metal ions from biomedical alloys, particularly Ni(2+) and Hg(2+), continue to be a concern. Heat-shock proteins (HSP) are a class of molecular chaperones that may be induced under conditions of cellular stress, including oxidative stress. Our hypothesis was that because Hg(2+) and Ni(2+) alter other cellular stress responses such as glutathione levels and cytokine secretion, these metal ions may alter HSP induction in monocytes, which are key cells in the response of tissues to biomedical alloys. THP-1 monocytes were exposed to sublethal concentrations of Hg(2+) or Ni(2+) for 1 h with or without heat stress (43 degrees C), then allowed to recover at 37 degrees C for 2-6 h. HSP72 was measured using immunoblotting with phosphorimage quantification. Hg(2+) exposures of 2-10 micromol/L induced HSP72 without heat stress. With heat stress, HSP72 levels were altered by Hg(2+) versus heat stress alone. The response depended on the concentration of Hg(2+) and the recovery time. Hg(2+) at 10 micromol/L caused uniformly lower HSP72 levels. Ni(2+) exposures of 20-100 micromol/L did not induce HSP72 without heat stress, but significantly altered heat-induced HSP72 expression, with a significant increase in expression over heat alone at 40 and 100 micromol/L. Results from the current study support the hypothesis that these metal ions can, at concentrations relevant to those released from biomedical alloys, modulate HSP expression in human monocytes. The modulation of HSP expression indicates an early sign of cellular stress that may be important to the overall biological response to biomedical alloys containing and releasing these metal ions.
生物医学合金释放金属离子，尤其是Ni(2+)和Hg(2+)所导致的生物学负担，仍然是一个令人担忧的问题。热休克蛋白（HSP）是一类分子伴侣，在包括氧化应激在内的细胞应激条件下可能会被诱导产生。我们的假设是，由于Hg(2+)和Ni(2+)会改变其他细胞应激反应，如谷胱甘肽水平和细胞因子分泌，这些金属离子可能会改变单核细胞中的HSP诱导，而单核细胞是组织对生物医学合金反应中的关键细胞。将THP-1单核细胞暴露于亚致死浓度的Hg(2+)或Ni(2+)中1小时，有无热应激（43摄氏度），然后在37摄氏度下恢复2至6小时。使用磷光图像定量免疫印迹法测量HSP72。2至10微摩尔/升的Hg(2+)暴露在无热应激的情况下诱导了HSP72。在有热应激的情况下，Hg(2+)与单独热应激相比改变了HSP72水平。该反应取决于Hg(2+)的浓度和恢复时间。10微摩尔/升的Hg(2+)导致HSP72水平一致降低。20至100微摩尔/升的Ni(2+)暴露在无热应激的情况下不会诱导HSP72，但显著改变了热诱导的HSP72表达，在40和100微摩尔/升时表达比单独热应激时有显著增加。当前研究的结果支持了这样的假设，即这些金属离子在与生物医学合金释放的浓度相关时，可以调节人单核细胞中的HSP表达。HSP表达的调节表明了细胞应激的早期迹象，这可能对含有并释放这些金属离子的生物医学合金的整体生物学反应很重要。
