Modifications of cell signalling in the cytotoxicity of metals.
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.
Rossi
A
A
Institute of Environmental Medicine, Karolinska Institutet. Stockholm, Sweden.
Manzo
L
L
Orrenius
S
S
Vahter
M
M
Nicotera
P
P
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D008670:Metals / Q000633:toxicity*; D015398:Signal Transduction / Q000187:drug effects*
D015220:Calcium Channels; D008670:Metals; D002118:Calcium