Rossi A, Manzo L, Orrenius S, Vahter M, Nicotera P
Institute of Environmental Medicine, Karolinska Institutet. Stockholm, Sweden.
Pharmacol Toxicol. 1991 Jun;68(6):424-9. doi: 10.1111/j.1600-0773.1991.tb01265.x.
Many metals act on biological systems at low concentrations and recent epidemiological and experimental research indicates that toxic effects of certain metals occur at levels only marginally higher than those found in healthy subjects. Despite a large number of studies describing metal cytotoxicity, the molecular mechanisms involved are still poorly understood. However, it now seems evident that several metals can interact with enzyme functional groups and that proteins involved in signal transduction, including Ca2+ channels and pumps, may be especially sensitive to this interaction. Impairment of the ability of cells to adequately respond to the stimulation by hormones and growth factors may result in the loss of important cell functions or activation of mechanisms that compromise cell survival. In the following sections we will briefly describe the effects of various metals on cell signalling and present our recent findings on the mechanism by which inorganic mercury affects signal transduction.
许多金属在低浓度时就会对生物系统产生作用,近期的流行病学和实验研究表明,某些金属的毒性作用发生时的浓度仅略高于健康受试者体内的浓度。尽管有大量研究描述了金属的细胞毒性,但其中涉及的分子机制仍知之甚少。然而,现在似乎很明显,几种金属可以与酶的官能团相互作用,并且参与信号转导的蛋白质,包括钙离子通道和泵,可能对这种相互作用特别敏感。细胞对激素和生长因子刺激做出充分反应的能力受损,可能会导致重要细胞功能的丧失或激活危及细胞存活的机制。在以下各节中,我们将简要描述各种金属对细胞信号传导的影响,并介绍我们最近关于无机汞影响信号转导机制的研究结果。