Mercuric chloride: toxicity and apoptosis in a human oligodendroglial cell line MO3.13.
A human-human oligodendroglial cell line MO3.13 was chosen in this study to model the loss of oligodendrocytes that occurs during episodes of multiple sclerosis. The influence of mercuric chloride (HgCl(2)) upon cell viability specifically the mode of cell death, whether by an active apoptotic mechanism or passive necrosis was determined by morphological and biochemical analysis. Mitochondrial dehydrogenase activity MTT assay showed that HgCl(2) had toxic effects on MO3.13 cells at levels of (5-25 microM) with approximately 50% cell death observed at 58 microM. Death of cells was dependent on both time and concentrations of HgCl(2). Differentiated MO3.13 cells exposed to low concentrations (25 microM) of HgCl(2) exhibited features of apoptotic cell death, including cell shrinkage and chromatin condensation. High doses of HgCl(2) (>100 microM) induced death with characteristics of necrosis. Biochemical analysis showed that HgCl(2) activated the caspase family of proteases. This was measured directly by cleavage of fluorescent substrates and by immunoblotting assay of caspase substrate proteins; alpha-fodrin, lamin B and poly (ADP-ribose) polymerase (PARP). These results indicate that HgCl(2) is toxic at low concentrations for oligodendroglial cells and that the MO3.13 cell line dies in an apoptotic manner when exposed to low concentrations of HgCl(2). However, blood mercury concentrations in vivo in a normal population with amalgam restorations are lower by a factor of some 500 times than those causing toxicity in vitro suggesting a good safety margin in respect of environmental uptake.
Issa
Y
Y
Turner Dental School, The University of Manchester, Manchester, UK.
Watts
D C
DC
Duxbury
A J
AJ
Brunton
P A
PA
Watson
M B
MB
Waters
C M
CM
D017209:Apoptosis / Q000187:drug effects*; D016923:Cell Death / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007700:Kinetics; D008627:Mercuric Chloride / Q000633:toxicity*; D008954:Models, Biological; D009103:Multiple Sclerosis / Q000473:pathology; D009836:Oligodendroglia / Q000166:cytology / Q000187:drug effects* / Q000473:pathology
D008627:Mercuric Chloride