Metallothionein in the central nervous system: Roles in protection, regeneration and cognition.
Neurotoxicology. 2008 May;29(3):489-503. doi: 10.1016/j.neuro.2007.12.006. Epub 2008 Jan 19.
PMID: 18313142
Free PMC article.
Review.
Metallothionein (MT) …
Metallothionein (MT) is an enigmatic protein, and its physiological role
remains a matter of intense study and debate 50 years after its
discovery. This is particularly true of its function in the central
nervous system (CNS), where the challenge remains to link its known
biochemical properties of metal binding and free radical scavenging to
the intricate workings of brain. In this compilation of four reports,
first delivered at the 11th International Neurotoxicology Association
(INA-11) Meeting, June 2007, the authors present the work of their
laboratories, each of which gives an important insight into the actions
of MT in the brain. What emerges is that MT has the potential to
contribute to a variety of processes, including neuroprotection,
regeneration, and even cognitive functions. In this article, the
properties and CNS expression of MT are briefly reviewed before Dr
Hidalgo describes his pioneering work using transgenic models of MT
expression to demonstrate how this protein plays a major role in the
defence of the CNS against neurodegenerative disorders and other CNS
injuries. His group's work leads to two further questions, what are the
mechanisms at the cellular level by which MT acts, and does this protein
influence higher order issues of architecture and cognition? These
topics are addressed in the second and third sections of this review by
Dr West, and Dr Levin and Dr Eddins, respectively. Finally, Dr Aschner
examines the ability of MT to protect against a specific toxicant,
methylmercury, in the CNS.
Toxicol In Vitro. 2010 Apr;24(3):835-41. doi: 10.1016/j.tiv.2009.12.009. Epub 2009 Dec 22.
PMID: 20005941
The knowledge of vascular toxicity is important for understanding the
neurotoxicity of methylmercury. In the present study, we investigated
the cell-density-dependent susceptibility of human brain microvascular
pericytes to methylmercury-induced toxicity by using a cell-culture
system. The susceptibility of sparse pericyte cultures to methylmercury
was greater than that of the dense cultures. In addition, the sparse
cultures were more susceptible to methylmercury than to inorganic
mercury and cadmium. The intracellular accumulation of methylmercury in
the sparse cells was significantly higher than that in the dense cells.
Methylmercury is transported through the L-type large neutral amino acid (LNAA)
transporter (LAT 1) in the form of a complex with cysteine. The mRNA-
and protein-level expressions of LAT 1 in the sparse cells were markedly
higher than those in the dense cells; in addition, the LAT 1 expression
was increased by methylmercury. However, there was no reduction in the
levels of glutathione and metallothionein, which are involved in the
defense mechanisms against methylmercury, in the sparse cells. The
present data revealed that pericytes are markedly susceptible to
methylmercury-induced cytotoxicity at low cell densities. The
susceptibility of the sparse pericytes is postulated to be due to the
not only constitutively higher but also methylmercury-induced expression
of LAT 1, which increased the intracellular accumulation of
methylmercury.
