Hg2+ and Ni2+ alter induction of heat shock protein-72 in THP-1 human monocytes.

Abstract

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.